Liver enzyme CYP2D6 gene and tardive dyskinesia

Author:

Lu Justin Y1,Tiwari Arun K12,Freeman Natalie1,Zai Gwyneth C123,Luca Vincenzo de123,Müller Daniel J123,Tampakeras Maria1,Herbert Deanna1,Emmerson Heather1,Cheema Sheraz Y1,King Nicole1,Voineskos Aristotle N123,Potkin Steven G4,Lieberman Jeffrey A5,Meltzer Herbert Y6,Remington Gary123,Kennedy James L123,Zai Clement C1237ORCID

Affiliation:

1. Tanenbaum Centre for Pharmacogenetics, Campbell Family Mental Health Research Institute, Centre for Addiction & Mental Health, Toronto, ON, M5T 1R8, Canada

2. Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8, Canada

3. Institute of Medical Science, University of Toronto, Toronto, ON, M5S 1A8, Canada

4. Department of Psychiatry & Human Behavior, Long Beach Veterans Administration Health Care System, University of California, Irvine, Irvine, CA 92617, USA

5. Department of Psychiatry, Columbia University College of Physicians & Surgeons, New York City, NY 10032, USA

6. Psychiatry & Behavioral Sciences, Pharmacology & Physiology, Chemistry of Life Processes Institute, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA

7. Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, M5S 1A8, Canada

Abstract

Background: Tardive dyskinesia (TD) is an iatrogenic involuntary movement disorder occurring after extended antipsychotic use with unclear pathogenesis. CYP2D6 is a liver enzyme involved in antipsychotic metabolism and a well-studied gene candidate for TD. Materials & methods: We tested predicted CYP2D6 metabolizer phenotype with TD occurrence and severity in our two samples of European chronic schizophrenia patients (total n = 198, of which 82 had TD). Results: TD occurrence were associated with extreme metabolizer phenotype, controlling for age and sex (p = 0.012). In other words, individuals with either increased and no CYP2D6 activity were at higher risk of having TD. Conclusion: Unlike most previous findings, TD occurrence may be associated with both extremes of CYP2D6 metabolic activity rather than solely for poor metabolizers.

Funder

Brain and Behavior Research Foundation

Centre for Addiction and Mental Health Foundation

Canadian Foundation for Innovation

National Institute of Mental Health

Canadian Institutes of Health Research

Genome Canada

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

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