| Title: |
Immunogenetics of lithium response and psychiatric phenotypes in patients with bipolar disorder |
| Authors: |
Herrera-Rivero, M; Gutiérrez-Fragoso, K; Kurtz, J; Baune, BT; Thalamuthu, A; Amare, AT; Adli, M; Akiyama, K; Akula, N; 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; Mitchell, Philip |
| Source: |
urn:ISSN:2158-3188 ; Translational Psychiatry, 14, 1, 174 |
| Publisher Information: |
Springer Nature |
| Publication Year: |
2024 |
| Collection: |
UNSW Sydney (The University of New South Wales): UNSWorks |
| Subject Terms: |
5202 Biological Psychology; 32 Biomedical and Clinical Sciences; 52 Psychology; Mental Illness; Genetics; Mental Health; Clinical Research; Serious Mental Illness; Bipolar Disorder; Brain Disorders; 2.1 Biological and endogenous factors; 3 Good Health and Well Being; Humans; Lithium; Retrospective Studies; Immunogenetics; Glycogen Synthase Kinase 3 beta; Phenotype; International Consortium on Lithium Genetics (ConLi+Gen); anzsrc-for: 5202 Biological Psychology; anzsrc-for: 32 Biomedical and Clinical Sciences; anzsrc-for: 52 Psychology; anzsrc-for: 1103 Clinical Sciences; anzsrc-for: 1117 Public Health and Health Services; anzsrc-for: 1701 Psychology; anzsrc-for: 3202 Clinical sciences; anzsrc-for: 3209 Neurosciences |
| Description: |
The link between bipolar disorder (BP) and immune dysfunction remains controversial. While epidemiological studies have long suggested an association, recent research has found only limited evidence of such a relationship. To clarify this, we performed an exploratory study of the contributions of immune-relevant genetic factors to the response to lithium (Li) treatment and the clinical presentation of BP. First, we assessed the association of a large collection of immune-related genes (4925) with Li response, defined by the Retrospective Assessment of the Lithium Response Phenotype Scale (Alda scale), and clinical characteristics in patients with BP from the International Consortium on Lithium Genetics (ConLi + Gen, N = 2374). Second, we calculated here previously published polygenic scores (PGSs) for immune-related traits and evaluated their associations with Li response and clinical features. Overall, we observed relatively weak associations (p < 1 × 10 −4 ) with BP phenotypes within immune-related genes. Network and functional enrichment analyses of the top findings from the association analyses of Li response variables showed an overrepresentation of pathways participating in cell adhesion and intercellular communication. These appeared to converge on the well-known Li-induced inhibition of GSK-3β. Association analyses of age-at-onset, number of mood episodes, and presence of psychosis, substance abuse and/or suicidal ideation suggested modest contributions of genes such as RTN4, XKR4, NRXN1, NRG1/3 and GRK5 to disease characteristics. PGS analyses returned weak associations (p < 0.05) between inflammation markers and the studied BP phenotypes. Our results suggest a modest relationship between immunity and clinical features in BP. More research is needed to assess the potential therapeutic relevance. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
https://hdl.handle.net/1959.4/103060 |
| DOI: |
10.1038/s41398-024-02865-4 |
| Availability: |
https://hdl.handle.net/1959.4/103060; https://unsworks.unsw.edu.au/bitstreams/1b630732-00db-4849-9289-fff202745b8a/download; https://doi.org/10.1038/s41398-024-02865-4 |
| 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.C6DC48CB |
| Database: |
BASE |