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

Leen Magarbeh^{1

2}, Claudia Hassel^{3

4}, Maximilian Choi^{1

2}, Farhana Islam^{1

2}, Victoria S Marshe^{1

5}, Clement C Zai^{1

6

7

8

9}, Rayyan Zuberi⁴, Roseann S Gammal¹⁰, Xiaoyu Men^{1

2}, Maike Scherf-Clavel¹¹, Dietmar Enko¹², Benicio N Frey^{13

14}, Roumen Milev¹⁵, Claudio N Soares¹⁵, Sagar V Parikh¹⁶, Franca Placenza¹⁷, Stephen C Strother¹⁸, Stefanie Hassel^{19

20}, Valerie H Taylor¹⁹, Francesco Leri²¹, Pierre Blier²², Faranak Farzan²³, Raymond W Lam²⁴, Gustavo Turecki²⁵, Jane A Foster^{13

17

26}, Susan Rotzinger²⁷, Stefan Kloiber^{1

2

6

7}, James L Kennedy^{1

6

7}, Sidney H Kennedy^{6

7

17

26

27}, Chad A Bousman^{4

19

28}, Daniel J Müller^{1

2

6

7

11}

Affiliations

¹ Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
² Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada.
³ Department of Life Sciences, Queen's University, Kingston, Ontario, Canada.
⁴ Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada.
⁵ Center for Translational and Computational Neuroimmunology, Columbia University Medical Center, New York, New York, USA.
⁶ Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
⁷ Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
⁸ Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
⁹ Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
¹⁰ Massachusetts College of Pharmacy and Health Sciences, Boston, Massachusetts, USA.
¹¹ Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany.
¹² Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
¹³ Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada.
¹⁴ Mood Disorders Program, St. Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada.
¹⁵ Department of Psychiatry, Queen's University, Providence Care, Kingston, Ontario, Canada.
¹⁶ Department of Psychiatry, University of Michigan, Ann Arbor, Michigan, USA.
¹⁷ Centre for Mental Health, University Health Network, Toronto, Ontario, Canada.
¹⁸ Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
¹⁹ Department of Psychiatry, University of Calgary, Calgary, Alberta, Canada.
²⁰ Mathison Centre for Mental Health Research and Education, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
²¹ Department of Psychology and Neuroscience, University of Guelph, Guelph, Ontario, Canada.
²² The Royal Institute of Mental Health Research, Ottawa, Ontario, Canada.
²³ Mechatronic Systems Engineering, Simon Fraser University, Surrey, British Columbia, Canada.
²⁴ Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada.
²⁵ McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Verdun, Quebec, Canada.
²⁶ Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada.
²⁷ Department of Psychiatry, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
²⁸ Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada.

PMID: 36681895
DOI: 10.1002/cpt.2854

Meta-Analysis

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

Leen Magarbeh et al. Clin Pharmacol Ther. 2023 Jul.

. 2023 Jul;114(1):88-117.

doi: 10.1002/cpt.2854. Epub 2023 Mar 6.

Authors

Affiliations

¹ Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
² Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada.
³ Department of Life Sciences, Queen's University, Kingston, Ontario, Canada.
⁴ Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada.
⁵ Center for Translational and Computational Neuroimmunology, Columbia University Medical Center, New York, New York, USA.
⁶ Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
⁷ Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
⁸ Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
⁹ Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
¹⁰ Massachusetts College of Pharmacy and Health Sciences, Boston, Massachusetts, USA.
¹¹ Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany.
¹² Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
¹³ Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada.
¹⁴ Mood Disorders Program, St. Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada.
¹⁵ Department of Psychiatry, Queen's University, Providence Care, Kingston, Ontario, Canada.
¹⁶ Department of Psychiatry, University of Michigan, Ann Arbor, Michigan, USA.
¹⁷ Centre for Mental Health, University Health Network, Toronto, Ontario, Canada.
¹⁸ Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
¹⁹ Department of Psychiatry, University of Calgary, Calgary, Alberta, Canada.
²⁰ Mathison Centre for Mental Health Research and Education, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
²¹ Department of Psychology and Neuroscience, University of Guelph, Guelph, Ontario, Canada.
²² The Royal Institute of Mental Health Research, Ottawa, Ontario, Canada.
²³ Mechatronic Systems Engineering, Simon Fraser University, Surrey, British Columbia, Canada.
²⁴ Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada.
²⁵ McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Verdun, Quebec, Canada.
²⁶ Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada.
²⁷ Department of Psychiatry, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
²⁸ Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada.

PMID: 36681895
DOI: 10.1002/cpt.2854

Abstract

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.

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References

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

Affiliations

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

Authors

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Abstract

References

Publication types

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LinkOut - more resources

Full Text Sources

Molecular Biology Databases