학술논문
Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.
Document Type
article
Author
Amare, Azmeraw; Thalamuthu, Anbupalam; Schubert, Klaus; Fullerton, Janice; Ahmed, Muktar; Hartmann, Simon; Papiol, Sergi; Heilbronner, Urs; Degenhardt, Franziska; Tekola-Ayele, Fasil; Hou, Liping; Hsu, Yi-Hsiang; Shekhtman, Tatyana; Adli, Mazda; Akula, Nirmala; Akiyama, Kazufumi; Ardau, Raffaella; Arias, Bárbara; Aubry, Jean-Michel; Hasler, Roland; Richard-Lepouriel, Hélène; Perroud, Nader; Backlund, Lena; Bhattacharjee, Abesh; Bellivier, Frank; Benabarre, Antonio; Bengesser, Susanne; Biernacka, Joanna; Birner, Armin; Marie-Claire, Cynthia; Cervantes, Pablo; Chen, Hsi-Chung; Chillotti, Caterina; Cichon, Sven; Cruceanu, Cristiana; Czerski, Piotr; Dalkner, Nina; Del Zompo, Maria; DePaulo, J; Étain, Bruno; Jamain, Stephane; Falkai, Peter; Forstner, Andreas; Frisen, Louise; Frye, Mark; Gard, Sébastien; Garnham, Julie; Goes, Fernando; Grigoroiu-Serbanescu, Maria; Fallgatter, Andreas; Stegmaier, Sophia; Ethofer, Thomas; Biere, Silvia; Petrova, Kristiyana; Schuster, Ceylan; Adorjan, Kristina; Budde, Monika; Heilbronner, Maria; Kalman, Janos; Kohshour, Mojtaba; Reich-Erkelenz, Daniela; Schaupp, Sabrina; Schulte, Eva; Senner, Fanny; Vogl, Thomas; Anghelescu, Ion-George; Arolt, Volker; Dannlowski, Udo; Dietrich, Detlef; Figge, Christian; Jäger, Markus; Lang, Fabian; Juckel, Georg; Konrad, Carsten; Reimer, Jens; Schmauß, Max; Schmitt, Andrea; Spitzer, Carsten; von Hagen, Martin; Wiltfang, Jens; Zimmermann, Jörg; Andlauer, Till; Fischer, Andre; Bermpohl, Felix; Ritter, Philipp; Matura, Silke; Gryaznova, Anna; Falkenberg, Irina; Yildiz, Cüneyt; Kircher, Tilo; Schmidt, Julia; Koch, Marius; Gade, Kathrin; Trost, Sarah; Haussleiter, Ida; Lambert, Martin; Rohenkohl, Anja; Kraft, Vivien; Grof, Paul; Hashimoto, Ryota
Source
Molecular Psychiatry. 28(12)
Subject
Language
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 lithiums 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