Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Amare, AT; Thalamuthu, A; Schubert, KO; Fullerton, JM; Ahmed, M; Hartmann, S; Papiol, S; Heilbronner, U; Degenhardt, F; Tekola-Ayele, F; Hou, L; Hsu, YH; Shekhtman, T; Adli, M; Akula, N; Akiyama, K; Ardau, R; Arias, B; Aubry, JM; Hasler, R; Richard-Lepouriel, H; Perroud, N; Backlund, L; Bhattacharjee, AK; Bellivier, F; Benabarre, A; Bengesser, S; Biernacka, JM; Birner, A; Marie-Claire, C; Cervantes, P; Chen, HC; Chillotti, C; Cichon, S; Cruceanu, C; Czerski, PM; Dalkner, N; Del, Zompo, M; DePaulo, JR; Étain, B; Jamain, S; Falkai, P; Forstner, AJ; Frisen, L; Frye, MA; Gard, S; Garnham, JS; Goes, FS; Grigoroiu-Serbanescu, M; Fallgatter, AJ; Stegmaier, S; Ethofer, T; Biere, S; Petrova, K; Schuster, C; Adorjan, K; Budde, M; Heilbronner, M; Kalman, JL; Kohshour, MO; Reich-Erkelenz, D; Schaupp, SK; Schulte, EC; Senner, F; Vogl, T; Anghelescu, IG; Arolt, V; Dannlowski, U; Dietrich, D; Figge, C; Jäger, M; Lang, FU; Juckel, G; Konrad, C; Reimer, J; Schmauß, M; Schmitt, A; Spitzer, C; von, Hagen, M; Wiltfang, J; Zimmermann, J; Andlauer, TFM; Fischer, A; Bermpohl, F; Ritter, P; Matura, S; Gryaznova, A; Falkenberg, I; Yildiz, C; Kircher, T; Schmidt, J; Koch, M; Gade, K; Trost, S; Haussleiter, IS; Lambert, M; Rohenkohl, AC; Kraft, V; Grof, P; Hashimoto, R; Hauser, J; Herms, S; Hoffmann, P; Jiménez, E; Kahn, JP; Kassem, L; Kuo, PH; Kato, T; Kelsoe, J; Kittel-Schneider, S; Ferensztajn-Rochowiak, E; König, B; Kusumi, I; Laje, G; Landén, M; Lavebratt, C; Leboyer, M; Leckband, SG; Tortorella, A; Manchia, M; Martinsson, L; McCarthy, MJ; McElroy, S; Colom, F; Millischer, V; Mitjans, M; Mondimore, FM; Monteleone, P; Nievergelt, CM; Nöthen, MM; Novák, T; O'Donovan, C; Ozaki, N; Pfennig, A; Pisanu, C; Potash, JB; Reif, A; Reininghaus, E; Rouleau, GA; Rybakowski, JK; Schalling, M; Schofield, PR; Schweizer, BW; Severino, G; Shilling, PD; Shimoda, K; Simhandl, C; Slaney, CM; Squassina, A; Stamm, T; Stopkova, P; Maj, M; Turecki, G; Vieta, E; Veeh, J; Witt, SH; Wright, A; Zandi, PP; Mitchell, PB; Bauer, M; Alda, M; Rietschel, M; McMahon, FJ; Schulze, TG; Clark, SR; Baune, BT.
Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.
Mol Psychiatry. 2023;
Doi: 10.1038/s41380-023-02149-1
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- Co-Autor*innen der Med Uni Graz
- Bengesser Susanne
- Birner Armin
- Dalkner Nina
- Reininghaus Eva
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- Abstract:
- Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N = 2367) and replicated in the combined PsyCourse (N = 89) and BipoLife (N = 102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P < 0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P = 9.8 × 10-12, R2 = 1.9%) and continuous (P = 6.4 × 10-9, R2 = 2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P = 3.9 × 10-4, R2 = 0.9%), but not for the continuous outcome (P = 0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.