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

Journal

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.

Authors with CRIS profile

Involved external institutions

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

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. Complex Psychiatry, 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." Complex Psychiatry 7.3-4 (2021): 80-89.

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