ABCB1 Gene Variants and Antidepressant Treatment Outcomes: A Systematic Review and Meta-Analysis Including Results from the CAN-BIND-1 Study.


Journal

Clinical pharmacology and therapeutics
ISSN: 1532-6535
Titre abrégé: Clin Pharmacol Ther
Pays: United States
ID NLM: 0372741

Informations de publication

Date de publication:
07 2023
Historique:
received: 04 11 2022
accepted: 06 01 2023
medline: 20 6 2023
pubmed: 23 1 2023
entrez: 22 1 2023
Statut: ppublish

Résumé

The P-glycoprotein efflux pump, encoded by the ABCB1 gene, has been shown to alter concentrations of various antidepressants in the brain. In this study, we conducted a systematic review and meta-analysis to investigate the association between six ABCB1 single-nucleotide polymorphisms (SNPs; rs1045642, rs2032582, rs1128503, rs2032583, rs2235015, and rs2235040) and antidepressant treatment outcomes in individuals with major depressive disorder (MDD), including new data from the Canadian Biomarker and Integration Network for Depression (CAN-BIND-1) cohort. For the CAN-BIND-1 sample, we applied regression models to investigate the association between ABCB1 SNPs and antidepressant treatment response, remission, tolerability, and antidepressant serum levels. For the meta-analysis, we systematically summarized pharmacogenetic evidence of the association between ABCB1 SNPs and antidepressant treatment outcomes. Studies were included in the meta-analysis if they investigated at least one ABCB1 SNP in individuals with MDD treated with at least one antidepressant. We did not find a significant association between ABCB1 SNPs and antidepressant treatment outcomes in the CAN-BIND-1 sample. A total of 39 studies were included in the systematic review. In the meta-analysis, we observed a significant association between rs1128503 and treatment response (T vs. C-allele, odds ratio = 1.30, 95% confidence interval = 1.15-1.48, P value (adjusted) = 0.024, n = 2,526). We did not find associations among the six SNPs and treatment remission nor tolerability. Our findings provide limited evidence for an association between common ABCB1 SNPs and antidepressant outcomes, which do not support the implementation of ABCB1 genotyping to inform antidepressant treatment at this time. Future research, especially on rs1128503, is recommended.

Identifiants

pubmed: 36681895
doi: 10.1002/cpt.2854
doi:

Substances chimiques

Antidepressive Agents 0
ATP Binding Cassette Transporter, Subfamily B, Member 1 0
Biomarkers 0
ABCB1 protein, human 0
ATP Binding Cassette Transporter, Subfamily B 0

Types de publication

Meta-Analysis Systematic Review Journal Article Review Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

88-117

Informations de copyright

© 2023 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.

Références

Trivedi, M.H. et al. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am. J. Psychiatry 163, 28-40 (2006).
Volkmann, C., Volkmann, A. & Muller, C.A. On the treatment effect heterogeneity of antidepressants in major depression: a Bayesian meta-analysis and simulation study. PLoS One. 15, e0241497 (2020).
Murphy, L.E., Fonseka, T.M., Bousman, C.A. & Muller, D.J. Gene-drug pairings for antidepressants and antipsychotics: level of evidence and clinical application. Mol. Psychiatry 27, 593-605 (2022).
Girardin, F. Membrane transporter proteins: a challenge for CNS drug development. Dialogues Clin. Neurosci. 8, 311-321 (2006).
Preskorn, S.H. Prediction of individual response to antidepressants and antipsychotics: an integrated concept. Dialogues Clin. Neurosci. 16, 545-554 (2014).
Bruckl, T.M. & Uhr, M. ABCB1 genotyping in the treatment of depression. Pharmacogenomics 17, 2039-2069 (2016).
Sharom, F.J. The P-glycoprotein multidrug transporter. Essays Biochem. 50, 161-178 (2011).
Pandit, R., Chen, L. & Gotz, J. The blood-brain barrier: physiology and strategies for drug delivery. Adv. Drug Deliv. Rev. 165-166, 1-14 (2020).
Doran, A. et al. The impact of P-glycoprotein on the disposition of drugs targeted for indications of the central nervous system: evaluation using the MDR1A/1B knockout mouse model. Drug Metab. Dispos. 33, 165-174 (2005).
Uhr, M., Steckler, T., Yassouridis, A. & Holsboer, F. Penetration of amitriptyline, but not of fluoxetine, into brain is enhanced in mice with blood-brain barrier deficiency due to mdr1a P-glycoprotein gene disruption. Neuropsychopharmacology 22, 380-387 (2000).
Wang, J.S. et al. Aripiprazole brain concentration is altered in P-glycoprotein deficient mice. Schizophr. Res. 110, 90-94 (2009).
O'Brien, F.E., Dinan, T.G., Griffin, B.T. & Cryan, J.F. Interactions between antidepressants and P-glycoprotein at the blood-brain barrier: clinical significance of in vitro and in vivo findings. Br. J. Pharmacol. 165, 289-312 (2012).
Wolf, S.J., Bachtiar, M., Wang, J., Sim, T.S., Chong, S.S. & Lee, C.G. An update on ABCB1 pharmacogenetics: insights from a 3D model into the location and evolutionary conservation of residues corresponding to SNPs associated with drug pharmacokinetics. Pharmacogenomics J. 11, 315-325 (2011).
Hoffmeyer, S. et al. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc. Natl. Acad. Sci. U. S. A. 97, 3473-3478 (2000).
Singh, A.B., Bousman, C.A., Ng, C.H., Byron, K. & Berk, M. ABCB1 polymorphism predicts escitalopram dose needed for remission in major depression. Transl. Psychiatry 2, e198 (2012).
Breitenstein, B. et al. Association of ABCB1 gene variants, plasma antidepressant concentration, and treatment response: results from a randomized clinical study. J. Psychiatr. Res. 73, 86-95 (2016).
Peters, E.J. et al. Pharmacokinetic genes do not influence response or tolerance to citalopram in the STAR*D sample. PLoS One. 3, e1872 (2008).
Lin, K.M. et al. ABCB1 gene polymorphisms are associated with the severity of major depressive disorder and its response to escitalopram treatment. Pharmacogenet. Genomics 21, 163-170 (2011).
Niitsu, T., Fabbri, C., Bentini, F. & Serretti, A. Pharmacogenetics in major depression: a comprehensive meta-analysis. Prog. Neuropsychopharmacol. Biol. Psychiatry 45, 183-194 (2013).
Uhr, M. et al. Polymorphisms in the drug transporter gene ABCB1 predict antidepressant treatment response in depression. Neuron 57, 203-209 (2008).
Mihaljevic, P.A., Bozina, N., Sagud, M., Rojnic, K.M. & Lovric, M. MDR1 gene polymorphism: therapeutic response to paroxetine among patients with major depression. Prog. Neuropsychopharmacol. Biol. Psychiatry 32, 1439-1444 (2008).
Menu, P., Gressier, F., Verstuyft, C., Hardy, P., Becquemont, L. & Corruble, E. Antidepressants and ABCB1 gene C3435T functional polymorphism: a naturalistic study. Neuropsychobiology 62, 193-197 (2010).
Breitenstein, B., Bruckl, T.M., Ising, M., Muller-Myhsok, B., Holsboer, F. & Czamara, D. ABCB1 gene variants and antidepressant treatment outcome: a meta-analysis. Am. J. Med. Genet. B Neuropsychiatr. Genet. 168B, 274-283 (2015).
Lam, R.W. et al. Discovering biomarkers for antidepressant response: protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort. BMC Psychiatry 16, 105 (2016).
Kennedy, S.H. et al. Symptomatic and functional outcomes and early prediction of response to Escitalopram monotherapy and sequential adjunctive aripiprazole therapy in patients with major depressive disorder: a CAN-BIND-1 report. J. Clin. Psychiatry 80, 2 (2019).
Islam, F. et al. Effects of CYP2C19 and CYP2D6 gene variants on escitalopram and aripiprazole treatment outcome and serum levels: results from the CAN-BIND 1 study. Transl. Psychiatry 12, 366 (2022).
Vanderkooy, J.D., Kennedy, S.H. & Bagby, R.M. Antidepressant side effects in depression patients treated in a naturalistic setting: a study of bupropion, moclobemide, paroxetine, sertraline, and venlafaxine. Can. J. Psychiatry 47, 174-180 (2002).
Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. Series B Stat. Methodol. 57, 289-300 (1995).
Moore, C.M., Jacobson, S.A. & Fingerlin, T.E. Power and sample size calculations for genetic association studies in the presence of genetic model misspecification. Hum. Hered. 84, 256-271 (2019).
Lenze, E.J. et al. Efficacy, safety, and tolerability of augmentation pharmacotherapy with aripiprazole for treatment-resistant depression in late life: a randomised, double-blind, placebo-controlled trial. Lancet 386, 2404-2412 (2015).
Scherf-Clavel, M. et al. Effects of pharmacokinetic gene variation on therapeutic drug levels and on antidepressant treatment response. Pharmacopsychiatry 55, 246-254 (2022).
Sterne, J.A. et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ 355, i4919 (2016).
Dalton, J.E., Bolen, S.D. & Mascha, E.J. Publication bias: the elephant in the review. Anesth. Analg. 123, 812-813 (2016).
Higgins, J.P.T. & Cochrane Collaboration Cochrane Handbook for Systematic Reviews of Interventions 2nd edn., Vol. xxviii. 694 (Wiley-Blackwell, Hoboken, NJ, 2020).
Borenstein, M., Hedges, L.V., Higgins, J.P. & Rothstein, H.R. Introduction to Meta-Analysis (John Wiley & Sons, 2011). https://doi.org/10.1002/9780470743386
Laika, B., Leucht, S. & Steimer, W. ABCB1 (P-glycoprotein/MDR1) gene G2677T/a sequence variation (polymorphism): lack of association with side effects and therapeutic response in depressed inpatients treated with amitriptyline. Clin. Chem. 52, 893-895 (2006).
Dong, C., Wong, M.L. & Licinio, J. Sequence variations of ABCB1, SLC6A2, SLC6A3, SLC6A4, CREB1, CRHR1 and NTRK2: association with major depression and antidepressant response in Mexican-Americans. Mol. Psychiatry 14, 1105-1118 (2009).
Perlis, R.H., Fijal, B., Dharia, S., Heinloth, A.N. & Houston, J.P. Failure to replicate genetic associations with antidepressant treatment response in duloxetine-treated patients. Biol. Psychiatry 67, 1110-1113 (2010).
Breitenstein, B. et al. The clinical application of ABCB1 genotyping in antidepressant treatment: a pilot study. CNS Spectr. 19, 165-175 (2014).
Gasso, P. et al. Effect of CYP2D6, CYP2C9 and ABCB1 genotypes on fluoxetine plasma concentrations and clinical improvement in children and adolescent patients. Pharmacogenomics J. 14, 457-462 (2014).
Ray, A. et al. ABCB1 (MDR1) predicts remission on P-gp substrates in chronic depression. Pharmacogenomics J. 15, 332-339 (2015).
Schatzberg, A.F., DeBattista, C., Lazzeroni, L.C., Etkin, A., Murphy, G.M. Jr. & Williams, L.M. ABCB1 genetic effects on antidepressant outcomes: a report from the iSPOT-D trial. Am. J. Psychiatry 172, 751-759 (2015).
Magalhaes, P., Alves, G., Fortuna, A., Llerena, A. & Falcao, A. Clinical collaborators of the Gn G.P.K.P.D.a.D.S. Pharmacogenetics and therapeutic drug monitoring of fluoxetine in a real-world setting: a PK/PD analysis of the influence of (non-)genetic factors. Exp. Clin. Psychopharmacol. 28, 589-600 (2020).
de Klerk, O.L. et al. ABCB1 gene variants influence tolerance to selective serotonin reuptake inhibitors in a large sample of Dutch cases with major depressive disorder. Pharmacogenomics J. 13, 349-353 (2013).
Bet, P.M. et al. A common polymorphism in the ABCB1 gene is associated with side effects of PGP-dependent antidepressants in a large naturalistic Dutch cohort. Pharmacogenomics J. 16, 202-208 (2016).
Crisafulli, C. et al. Case-control association study of 36 single-nucleotide polymorphisms within 10 candidate genes for major depression and bipolar disorder. Psychiatry Res. 209, 121-123 (2013).
Huang, X. et al. ABCB6, ABCB1 and ABCG1 genetic polymorphisms and antidepressant response of SSRIs in Chinese depressive patients. Pharmacogenomics 14, 1723-1730 (2013).
Vancova, Z., Cizmarikova, M., Dragasek, J., Zofcakova, S., Kolarcik, P. & Mojzis, J. Does G2677T polymorphism of the MDR1 gene make a difference in the therapeutic response to paroxetine in depressed patients in a Slovakian population? Med. Sci. Monit. 24, 3136-3145 (2018).
Roberts, R.L., Joyce, P.R., Mulder, R.T., Begg, E.J. & Kennedy, M.A. A common P-glycoprotein polymorphism is associated with nortriptyline-induced postural hypotension in patients treated for major depression. Pharmacogenomics J. 2, 191-196 (2002).
Gex-Fabry, M. et al. CYP2D6 and ABCB1 genetic variability: influence on paroxetine plasma level and therapeutic response. Ther. Drug Monit. 30, 474-482 (2008).
Ozbey, G. et al. ABCB1 C3435T polymorphism is associated with susceptibility to major depression, but not with a clinical response to citalopram in a Turkish population. Pharmacol. Rep. 66, 235-238 (2014).
Wolking, S., Schaeffeler, E., Lerche, H., Schwab, M. & Nies, A.T. Impact of genetic polymorphisms of ABCB1 (MDR1, P-glycoprotein) on drug disposition and potential clinical implications: update of the literature. Clin. Pharmacokinet. 54, 709-735 (2015).
Fung, K.L. & Gottesman, M.M. A synonymous polymorphism in a common MDR1 (ABCB1) haplotype shapes protein function. Biochim. Biophys. Acta 1794, 860-871 (2009).
Kimchi-Sarfaty, C. et al. A "silent" polymorphism in the MDR1 gene changes substrate specificity. Science 315, 525-528 (2007).
Hung, C.C., Chen, C.C., Lin, C.J. & Liou, H.H. Functional evaluation of polymorphisms in the human ABCB1 gene and the impact on clinical responses of antiepileptic drugs. Pharmacogenet. Genomics 18, 390-402 (2008).
Shan, X.X. et al. ABCB1 gene is associated with clinical response to SNRIs in a local Chinese Han population. Front. Pharmacol. 10, 761 (2019).
Simoons, M. et al. Modification of the association between paroxetine serum concentration and SERT-occupancy by ABCB1 (P-glycoprotein) polymorphisms in major depressive disorder. Psychiatr. Genet. 30, 19-29 (2020).
Moncrieff, J. A comparison of antidepressant trials using active and inert placebos. Int. J. Methods Psychiatr. Res. 12, 117-127 (2003).
Maruf, A.A., Fan, M., Arnold, P.D., Muller, D.J., Aitchison, K.J. & Bousman, C.A. Pharmacogenetic testing options relevant to psychiatry in Canada: options de tests pharmacogenetiques pertinents en psychiatrie au Canada. Can. J. Psychiatry 65, 521-530 (2020).
Singh, A.B. Improved antidepressant remission in major depression via a pharmacokinetic pathway polygene Pharmacogenetic report. Clin. Psychopharmacol. Neurosci. 13, 150-156 (2015).
Bousman, C.A. & Hopwood, M. Commercial pharmacogenetic-based decision-support tools in psychiatry. Lancet Psychiatry 3, 585-590 (2016).
Kato, M. et al. ABCB1 (MDR1) gene polymorphisms are associated with the clinical response to paroxetine in patients with major depressive disorder. Prog. Neuropsychopharmacol. Biol. Psychiatry 32, 398-404 (2008).
Nikisch, G., Eap, C.B. & Baumann, P. Citalopram enantiomers in plasma and cerebrospinal fluid of ABCB1 genotyped depressive patients and clinical response: a pilot study. Pharmacol. Res. 58, 344-347 (2008).
Sarginson, J.E., Lazzeroni, L.C., Ryan, H.S., Ershoff, B.D., Schatzberg, A.F. & Murphy, G.M. Jr. ABCB1 (MDR1) polymorphisms and antidepressant response in geriatric depression. Pharmacogenet. Genomics 20, 467-475 (2010).
Perroud, N. et al. Clinical and genetic correlates of suicidal ideation during antidepressant treatment in a depressed outpatient sample. Pharmacogenomics 12, 365-377 (2011).
Bly, M.J., Bishop, J.R., Thomas, K.L. & Ellingrod, V.L. P-glycoprotein (PGP) polymorphisms and sexual dysfunction in female patients with depression and SSRI-associated sexual side effects. J. Sex Marital Ther. 39, 280-288 (2013).
Blazquez, A., Gasso, P., Mas, S., Plana, M.T., Lafuente, A. & Lazaro, L. One-year follow-up of children and adolescents with major depressive disorder: relationship between clinical variables and Abcb1 gene polymorphisms. Pharmacopsychiatry 49, 248-253 (2016).
Chang, H.H., Chou, C.H., Yang, Y.K., Lee, I.H. & Chen, P.S. Association between ABCB1 polymorphisms and antidepressant treatment response in Taiwanese major depressive patients. Clin. Psychopharmacol. Neurosci. 13, 250-255 (2015).
Jelen, A.M. et al. The influence of C3435T polymorphism of the ABCB1 gene on genetic susceptibility to depression and treatment response in polish population - preliminary report. Int. J. Med. Sci. 12, 974-979 (2015).
Ozbey, G. et al. Influence of ABCB1 polymorphisms and serum concentrations on venlafaxine response in patients with major depressive disorder. Nord. J. Psychiatry 71, 230-237 (2017).
Bousman, C.A., Muller, D.J., Ng, C.H., Byron, K., Berk, M. & Singh, A.B. Concordance between actual and pharmacogenetic predicted desvenlafaxine dose needed to achieve remission in major depressive disorder: a 10-week open-label study. Pharmacogenet. Genomics 27, 1-6 (2017).
Geers, L.M. et al. Influence of eight ABCB1 polymorphisms on antidepressant response in a prospective cohort of treatment-free Russian patients with moderate or severe depression: an explorative psychopharmacological study with naturalistic design. Hum. Psychopharmacol. 37, e2826 (2022).

Auteurs

Leen Magarbeh (L)

Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada.

Claudia Hassel (C)

Department of Life Sciences, Queen's University, Kingston, Ontario, Canada.
Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada.

Maximilian Choi (M)

Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada.

Farhana Islam (F)

Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada.

Victoria S Marshe (VS)

Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Center for Translational and Computational Neuroimmunology, Columbia University Medical Center, New York, New York, USA.

Clement C Zai (CC)

Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.

Rayyan Zuberi (R)

Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada.

Roseann S Gammal (RS)

Massachusetts College of Pharmacy and Health Sciences, Boston, Massachusetts, USA.

Xiaoyu Men (X)

Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada.

Maike Scherf-Clavel (M)

Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany.

Dietmar Enko (D)

Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.

Benicio N Frey (BN)

Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada.
Mood Disorders Program, St. Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada.

Roumen Milev (R)

Department of Psychiatry, Queen's University, Providence Care, Kingston, Ontario, Canada.

Claudio N Soares (CN)

Department of Psychiatry, Queen's University, Providence Care, Kingston, Ontario, Canada.

Sagar V Parikh (SV)

Department of Psychiatry, University of Michigan, Ann Arbor, Michigan, USA.

Franca Placenza (F)

Centre for Mental Health, University Health Network, Toronto, Ontario, Canada.

Stephen C Strother (SC)

Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.

Stefanie Hassel (S)

Department of Psychiatry, University of Calgary, Calgary, Alberta, Canada.
Mathison Centre for Mental Health Research and Education, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.

Valerie H Taylor (VH)

Department of Psychiatry, University of Calgary, Calgary, Alberta, Canada.

Francesco Leri (F)

Department of Psychology and Neuroscience, University of Guelph, Guelph, Ontario, Canada.

Pierre Blier (P)

The Royal Institute of Mental Health Research, Ottawa, Ontario, Canada.

Faranak Farzan (F)

Mechatronic Systems Engineering, Simon Fraser University, Surrey, British Columbia, Canada.

Raymond W Lam (RW)

Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada.

Gustavo Turecki (G)

McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Verdun, Quebec, Canada.

Jane A Foster (JA)

Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada.
Centre for Mental Health, University Health Network, Toronto, Ontario, Canada.
Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada.

Susan Rotzinger (S)

Department of Psychiatry, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.

Stefan Kloiber (S)

Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada.
Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.

James L Kennedy (JL)

Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.

Sidney H Kennedy (SH)

Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Centre for Mental Health, University Health Network, Toronto, Ontario, Canada.
Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada.
Department of Psychiatry, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.

Chad A Bousman (CA)

Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada.
Department of Psychiatry, University of Calgary, Calgary, Alberta, Canada.
Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada.

Daniel J Müller (DJ)

Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada.
Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany.

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