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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)80-89
Number of pages10
JournalComplex Psychiatry
Volume7
Issue number3-4
DOIs
StatePublished - Dec 1 2021

Keywords

  • Adherence
  • Attention-deficit/hyperactivity disorder
  • Bipolar disorder
  • Lithium response
  • Polygenic risk scores

ASJC Scopus subject areas

  • Psychology (miscellaneous)

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