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 Bengesser; Abesh 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

doi:10.1159/000519707

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 Bengesser

Abesh 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

Mayo Clinic Rochester, MN
Medical University of Vienna
Karolinska Institutet
National Institutes of Health
Ludwig Maximilian University of Munich
Charité – Universitätsmedizin Berlin
Dokkyo Medical University
University of Adelaide
South Australian Health And Medical Research Institute
University of Cagliari
University of Barcelona
University of Geneva
Technische Universität Dresden
University of Münster
University of Melbourne
INSERM UMR-S 1144—Université Paris Cité Département de Psychiatrie et de Médecine Addictologique
Medical University of Graz
University of California at San Diego
McGill University
National Taiwan University
University of Basel
Jülich Research Centre
Hospital del Mar
Instituto de Salud Carlos III
Douglas Mental Health University Institute
University of Medical Sciences Poznan
University of Bonn
Johns Hopkins University
University of Marburg
Hôpital Charles Perrens
Dalhousie University
Alexandru Obregia Clinical Psychiatric Hospital
Mood Disorders Center of Ottawa
National Center of Neurology and Psychiatry Kodaira
The University of Osaka
Université de Lorraine
Juntendo University
Goethe University Frankfurt
Landesklinikum Neunkirchen
Hokkaido University
University of Gothenburg
Hôpital Henri Mondor
Université Paris-Est-Créteil
Fondation FondaMental
Department of Veterans Affairs
University of Campania Luigi Vanvitelli
University of Cincinnati
University of New South Wales
University of Salerno
National Institute of Mental Health
Nagoya University
Heidelberg University
Neuroscience Research Australia
Mental Health Services
Sigmund Freud University Vienna
University of Perugia
University of Göttingen

Research output: Contribution to journal › Article › peer-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 language	English
Pages (from-to)	80-89
Number of pages	10
Journal	Complex Psychiatry
Volume	7
Issue number	3-4
DOIs	https://doi.org/10.1159/000519707
Publication status	Published - 1 Dec 2021
Externally published	Yes

Keywords

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

Access to Document

10.1159/000519707

Cite this

Coombes, B. J., Millischer, V., Batzler, A., Larrabee, B., Hou, L., Papiol, S., Heilbronner, U., Adli, M., Akiyama, K., Akula, N., Amare, A. T., Ardau, R., Arias, B., Aubry, J. M., Backlund, L., Bauer, M., Baune, B. T., Bellivier, F., Benabarre, A., ... 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

@article{6204edb7473a487ca15b9d3252f25ec3,

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

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.",

keywords = "Adherence, Attention-deficit/hyperactivity disorder, Bipolar disorder, Lithium response, Polygenic risk scores",

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

year = "2021",

month = dec,

day = "1",

doi = "10.1159/000519707",

language = "English",

volume = "7",

pages = "80--89",

journal = "Complex Psychiatry",

issn = "2673-3005",

publisher = "S. Karger AG",

number = "3-4",

}

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, 'Association of Attention-Deficit/Hyperactivity Disorder and Depression Polygenic Scores with Lithium Response: A Consortium for Lithium Genetics Study', Complex Psychiatry, vol. 7, no. 3-4, pp. 80-89. https://doi.org/10.1159/000519707

TY - JOUR

T1 - Association of Attention-Deficit/Hyperactivity Disorder and Depression Polygenic Scores with Lithium Response

T2 - A Consortium for Lithium Genetics Study

AU - Coombes, Brandon J.

AU - Millischer, Vincent

AU - Batzler, Anthony

AU - Larrabee, Beth

AU - Hou, Liping

AU - Papiol, Sergi

AU - Heilbronner, Urs

AU - Adli, Mazda

AU - Akiyama, Kazufumi

AU - Akula, Nirmala

AU - Amare, Azmeraw T.

AU - Ardau, Raffaella

AU - Arias, Barbara

AU - Aubry, Jean Michel

AU - Backlund, Lena

AU - Bauer, Michael

AU - Baune, Bernhard T.

AU - Bellivier, Frank

AU - Benabarre, Antoni

AU - Bengesser, Susanne

AU - Bhattacharjee, Abesh Kumar

AU - Cervantes, Pablo

AU - Chen, Hsi Chung

AU - Chillotti, Caterina

AU - Cichon, Sven

AU - Clark, Scott R.

AU - Colom, Francesc

AU - Cruceanu, Cristiana

AU - Czerski, Piotr M.

AU - Dalkner, Nina

AU - Degenhardt, Franziska

AU - Zompo, Maria Del

AU - Raymond DePaulo, J.

AU - Étain, Bruno

AU - Falkai, Peter

AU - Ferensztajn-Rochowiak, Ewa

AU - Forstner, Andreas J.

AU - Frisen, Louise

AU - Gard, Sébastien

AU - Garnham, Julie S.

AU - Goes, Fernando S.

AU - Grigoroiu-Serbanescu, Maria

AU - Grof, Paul

AU - Hashimoto, Ryota

AU - Hauser, Joanna

AU - Herms, Stefan

AU - Hoffmann, Per

AU - Jamain, Stephane

AU - Jiménez, Esther

AU - Kahn, Jean Pierre

AU - Kassem, Layla

AU - Kato, Tadafumi

AU - Kelsoed, John R.

AU - Kittel-Schneider, Sarah

AU - König, Barbara

AU - Kuo, Po Hsiu

AU - Kusumi, Ichiro

AU - Landén, Gonzalo Lajed Mikael

AU - Lavebratt, Catharina

AU - Leboyer, Marion

AU - Leckband, Susan G.

AU - Maj, Mario

AU - Manchia, Mirko

AU - Martinsson, Lina

AU - McCarthy, Michael J.

AU - McElroy, Susan L.

AU - Mitchell, Philip B.

AU - Mitjans, Marina

AU - Mondimore, Francis M.

AU - Monteleone, Palmiero

AU - Nievergelt, Caroline M.

AU - Nöthen, Markus M.

AU - Novák, Tomas

AU - O'Donovan, Claire

AU - Osby, Urban

AU - Ozaki, Norio

AU - Pfennig, Andrea

AU - Pisanu, Claudia

AU - Potash, James B.

AU - Reif, Andreas

AU - Reininghaus, Eva

AU - Rietschel, Marcella

AU - Rouleau, Guy A.

AU - Rybakowski, Janusz K.

AU - Schalling, Martin

AU - Schofield, Peter R.

AU - Schuberti, Klaus Oliver

AU - Schweizer, Barbara W.

AU - Severino, Giovanni

AU - Shekhtman, Tatyana

AU - Shilling, Paul D.

AU - Shimoda, Katzutaka

AU - Simhandl, Christian

AU - Slaney, Claire M.

AU - Squassina, Alessio

AU - Stamm, Thomas

AU - Stopkova, Pavla

AU - Tortorella, Alfonso

AU - Turecki, Gustavo

AU - Vieta, Eduard

AU - Witt, Stephanie H.

AU - Zandi, Peter P.

AU - Fullerton, Janice M.

AU - Alda, Martin

AU - Frye, Mark A.

AU - Schulze, Thomas G.

AU - McMahon, Francis J.

AU - Biernacka, Joanna M.

PY - 2021/12/1

Y1 - 2021/12/1

N2 - 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.

AB - 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.

KW - Adherence

KW - Attention-deficit/hyperactivity disorder

KW - Bipolar disorder

KW - Lithium response

KW - Polygenic risk scores

UR - https://www.scopus.com/pages/publications/85123614695

U2 - 10.1159/000519707

DO - 10.1159/000519707

M3 - Article

AN - SCOPUS:85123614695

SN - 2673-3005

VL - 7

SP - 80

EP - 89

JO - Complex Psychiatry

JF - Complex Psychiatry

IS - 3-4

ER -

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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this