Liver enzyme CYP2D6 gene and tardive dyskinesia

Justin Y. Lu, Arun K. Tiwari, Natalie Freeman, Gwyneth C. Zai, Vincenzo De Luca, Daniel J. Müller, Maria Tampakeras, Deanna Herbert, Heather Emmerson, Sheraz Y. Cheema, Nicole King, Aristotle N. Voineskos, Steven G. Potkin, Jeffrey A. Lieberman, Herbert Y. Meltzer, Gary Remington, James L. Kennedy, Clement C. Zai*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1065-1072
Number of pages8
JournalPharmacogenomics
Volume21
Issue number15
DOIs
StatePublished - Oct 2020

Keywords

  • CYP2D6
  • metabolizer phenotype
  • pharmacogenetics
  • schizophrenia
  • tardive dyskinesia

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

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