Association of Attention-Deficit/Hyperactivity Disorder and Depression Polygenic Scores with Lithium Response: A Consortium for Lithium Genetics Study

Coombes BJ, Millischer V, Batzler A, Larrabee B, Hou L, Papiol S, Heilbronner U, Adli M, Akiyama K, Akula N, Amare AT, Ardau R, Arias B, Aubry JM, Backlund L, Bauer M, Baune BT, Bellivier F, Benabarre A, Bengesser S, Bhattacharjee AK, Cervantes P, Chen HC, Chillotti C, Cichon S, Clark SR, Colom F, Cruceanu C, Czerski PM, Dalkner N, Degenhardt F, Zompo MD, Raymond DePaulo J, Étain B, Falkai P, Ferensztajn-Rochowiak E, Forstner AJ, Frisen L, Gard S, Garnham JS, Goes FS, Grigoroiu-Serbanescu M, Grof P, Hashimoto R, Hauser J, Herms S, Hoffmann P, Jamain S, Jiménez E, Kahn JP, Kassem L, Kato T, Kelsoed JR, Kittel-Schneider S, König B, Kuo PH, Kusumi I, Landén GLM, Lavebratt C, Leboyer M, Leckband SG, Maj M, Manchia M, Martinsson L, McCarthy MJ, McElroy SL, Mitchell PB, Mitjans M, Mondimore FM, Monteleone P, Nievergelt CM, Nöthen MM, Novák T, O'Donovan C, Osby U, Ozaki N, Pfennig A, Pisanu C, Potash JB, Reif A, Reininghaus E, Rietschel M, Rouleau GA, Rybakowski JK, Schalling M, Schofield PR, Schuberti KO, Schweizer BW, Severino G, Shekhtman T, Shilling PD, Shimoda K, Simhandl C, Slaney CM, Squassina A, Stamm T, Stopkova P, Tortorella A, Turecki G, Vieta E, Witt SH, Zandi PP, Fullerton JM, Alda M, Frye MA, Schulze TG, McMahon FJ, Biernacka JM (2021)

Publication Type: Journal article

Publication year: 2021

Book Volume: 7

Pages Range: 80-89

Journal Issue: 3-4

DOI: 10.1159/000519707

Abstract

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 longterm 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.

Involved external institutions

Medizinische Universität Wien Austria (AT) Mayo Clinic United States (USA) (US) University of New South Wales (UNSW) Australia (AU) Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) Spain (ES) Universitat de Barcelona (UB) / University of Barcelona Spain (ES) Johns Hopkins University (JHU) United States (USA) (US) Karolinska Institute Sweden (SE) South Australian Health and Medical Research Institute (SAHMRI) Australia (AU) Università degli Studi di Salerno Italy (IT) National Institute of Mental Health Information Resource Center United States (USA) (US) Dokkyo Medical University Japan (JP) Sigmund-Freud-Privatuniversität Wien (SFU) / Sigmund Freud University Austria (AT) Charité - Universitätsmedizin Berlin Germany (DE) Geneva University Hospitals / Hôpitaux universitaires de Genève (HUG) Switzerland (CH) University of Adelaide Australia (AU) National Institute of Mental Health (NIMH) / Národní ústav duševního zdraví (NUDZ) Czech Republic (CZ) Poznan University of Medical Sciences / Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu Poland (PL) Universitätsklinikum Mannheim / University Medical Centre Mannheim (Universitätsmedizin Mannheim) Germany (DE) Philipps-Universität Marburg Germany (DE) Klinikum der Universität München (LMU Klinikum) Germany (DE) Universitätsklinikum Bonn Germany (DE) Università degli Studi di Cagliari Italy (IT) Université Paris Cité France (FR) Universitätsklinikum Carl Gustav Carus Dresden Germany (DE) Westfälische Wilhelms-Universität (WWU) Münster Germany (DE) Douglas Mental Health University Institute Canada (CA) Universitätsspital Basel Switzerland (CH) Hospital del Mar Spain (ES) Université de Lorraine France (FR) Forschungszentrum Jülich / Research Centre Jülich (FZJ) Germany (DE) Juntendo University Japan (JP) Universitätsklinikum Frankfurt am Main (KGU) Germany (DE) Centre Hospitalier Charles Perrens (CHCP) France (FR) Dalhousie University Canada (CA) Medizinische Universität Graz Austria (AT) Montreal Neurological Institute and Hospital (MNI, The Neuro) Canada (CA) Neuroscience Research Australia NeuRA Australia (AU) Karolinska University Hospital / Karolinska Universitetssjukhuset Sweden (SE) National Taiwan University (NTU) Taiwan (TW) Centre hospitalier universitaire Henri-Mondor (CHU Henri-Mondor) France (FR) Paris-Est Créteil University / Université Paris-Est Créteil Val-de-Marne (UPEC) / Université Paris XII-Val-de-Marne / University Paris 12 Marne la Vallée France (FR) University of California, San Diego (UC San Diego, UCSD) United States (USA) (US) VA San Diego Healthcare System United States (USA) (US) McGill University Health Centre (MUHC) / Centre universitaire de santé McGill Canada (CA) National Taiwan University Hospital (NTUH) / 國立台灣大學醫學院附設醫院 Taiwan (TW) Mood Disorders Ottawa Canada (CA)

How to cite

APA:

Coombes, B.J., Millischer, V., Batzler, A., Larrabee, B., Hou, L., Papiol, S.,... Biernacka, J.M. (2021). Association of Attention-Deficit/Hyperactivity Disorder and Depression Polygenic Scores with Lithium Response: A Consortium for Lithium Genetics Study. , 7(3-4), 80-89. https://doi.org/10.1159/000519707

MLA:

Coombes, Brandon J., et al. "Association of Attention-Deficit/Hyperactivity Disorder and Depression Polygenic Scores with Lithium Response: A Consortium for Lithium Genetics Study." 7.3-4 (2021): 80-89.

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