Association of Attention-Deficit/Hyperactivity Disorder and Depression Polygenic Scores with Lithium Response: A Consortium for Lithium Genetics Study
Creators: name: Coombes, Brandon J.
name: Millischer, Vincent
name: Batzler, Anthony
name: Larrabee, Beth
name: Hou, Liping
name: Papiol, Sergi
name: Heilbronner, Urs
name: Adli, Mazda
name: Akiyama, Kazufumi
name: Akula, Nirmala
name: Amare, Azmeraw T.
name: Ardau, Raffaella
name: Arias, Barbara
name: Aubry, Jean-Michel
name: Backlund, Lena
name: Bauer, Michael
name: Baune, Bernhard T.
name: Bellivier, Frank
name: Benabarre, Antoni
name: Bengesser, Susanne
name: Bhattacharjee, Abesh Kumar
name: Cervantes, Pablo
name: Chen, Hsi-Chung
name: Chillotti, Caterina
name: Cichon, Sven
name: Clark, Scott R.
name: Colom, Francesc
name: Cruceanu, Cristiana
name: Czerski, Piotr M.
name: Dalkner, Nina
name: Degenhardt, Franziska
name: Del Zompo, Maria
name: DePaulo, J. Raymond
name: Étain, Bruno
name: Falkai, Peter
name: Ferensztajn-Rochowiak, Ewa
name: Forstner, Andreas J.
name: Frisen, Louise
name: Gard, Sébastien
name: Garnham, Julie S.
name: Goes, Fernando S.
name: Grigoroiu-Serbanescu, Maria
name: Grof, Paul
name: Hashimoto, Ryota
name: Hauser, Joanna
name: Herms, Stefan
name: Hoffmann, Per
name: Jamain, Stephane
name: Jiménez, Esther
name: Kahn, Jean-Pierre
name: Kassem, Layla
name: Kato, Tadafumi
name: Kelsoe, John R.
name: Kittel-Schneider, Sarah
name: König, Barbara
name: Kuo, Po-Hsiu
name: Kusumi, Ichiro
name: Laje, Gonzalo
name: Landén, Mikael
name: Lavebratt, Catharina
name: Leboyer, Marion
name: Leckband, Susan G.
name: Maj, Mario
name: Manchia, Mirko
name: Martinsson, Lina
name: McCarthy, Michael J.
name: McElroy, Susan L.
name: Mitchell, Philip B.
name: Mitjans, Marina
name: Mondimore, Francis M.
name: Monteleone, Palmiero
name: Nievergelt, Caroline M.
name: Nöthen, Markus M.
name: Novák, Tomas
name: O’Donovan, Claire
name: Osby, Urban
name: Ozaki, Norio
name: Pfennig, Andrea
name: Pisanu, Claudia
name: Potash, James B.
name: Reif, Andreas
name: Reininghaus, Eva
name: Rietschel, Marcella
name: Rouleau, Guy A.
name: Rybakowski, Janusz K.
name: Schalling, Martin
name: Schofield, Peter R.
name: Schubert, Klaus Oliver
name: Schweizer, Barbara W.
name: Severino, Giovanni
name: Shekhtman, Tatyana
name: Shilling, Paul D.
name: Shimoda, Katzutaka
name: Simhandl, Christian
name: Slaney, Claire M.
name: Squassina, Alessio
name: Stamm, Thomas
name: Stopkova, Pavla
name: Tortorella, Alfonso
name: Turecki, Gustavo
name: Vieta, Eduard
name: Witt, Stephanie H.
name: Zandi, Peter P.
name: Fullerton, Janice M.
name: Alda, Martin
name: Frye, Mark A.
name: Schulze, Thomas G.
name: McMahon, Francis J.
name: Biernacka, Joanna M.
Publisher: name: Charité - Universitätsmedizin Berlin
Year: 2021
Subjects: subject: Bipolar disorder
subject: Lithium response
subject: Polygenic risk scores
subject: Attention-deficit/hyperactivity disorder
subject: Adherence
subject: 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit

description: Response to lithium varies widely between individuals with bipolar disorder (BD). Polygenic risk scores (PRSs) can uncover pharmacogenomics effects and may help predict drug response. Patients (N = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), and schizophrenia (SCZ) were computed using lassosum and in a model including all three PRSs and other covariates, and the PRS of ADHD (β = −0.14; 95% confidence interval [CI]: −0.24 to −0.03; p value = 0.010) and MDD (β = −0.16; 95% CI: −0.27 to −0.04; p value = 0.005) predicted worse quantitative lithium response. A higher SCZ PRS was associated with higher rates of medication nonadherence (OR = 1.61; 95% CI: 1.34–1.93; p value = 2e−7). This study indicates that genetic risk for ADHD and depression may influence lithium treatment response. Interestingly, a higher SCZ PRS was associated with poor adherence, which can negatively impact treatment response. Incorporating genetic risk of ADHD, depression, and SCZ in combination with clinical risk may lead to better clinical care for patients with BD.