Genetic study of BDNF, DRD3, and their interaction in tardive dyskinesia

Clement C. Zai, Arun K. Tiwari, Vincenzo De Luca, Daniel J. Müller, Natalie Bulgin, Rudi Hwang, Gwyneth C. Zai, Nicole King, Aristotle N. Voineskos, Herbert Y. Meltzer, Jeffrey A. Lieberman, Steven G. Potkin, Gary Remington, James L. Kennedy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Tardive dyskinesia (TD) is a neuroleptic-induced movement disorder. Its pathophysiology is unclear. The most consistent genetic findings have shown an association with the Ser9Gly polymorphism of the DRD3 gene. However, only few polymorphisms within DRD3 has been tested, and a comprehensive examination of DRD3 in TD is still lacking. Further, brain-derived neurotrophic factor (BDNF), a neuronal growth and survival peptide, regulates DRD3 expression and may be involved in the neuronal degeneration observed in TD. In the present study, we investigated 15 tag DRD3 polymorphisms and four tag BDNF polymorphisms for association with TD in our sample of Caucasian schizophrenia patients (N = 171). While BDNF markers showed no association, a haplotype containing rs3732782, rs905568, and rs7620754 in the 5′ region of DRD3 was associated with TD diagnosis (p[10,000 permutations] = 0.007). We also found evidence of interaction between BDNF and DRD3 polymorphisms. Further studies are needed to confirm these findings.

Original languageEnglish (US)
Pages (from-to)317-328
Number of pages12
JournalEuropean Neuropsychopharmacology
Volume19
Issue number5
DOIs
StatePublished - May 2009

Funding

Funding for this study was provided in part by the Canadian Institute for Health Research (CIHR) MOP79525, the Bebensee Foundation, the C. R. Younger Foundation, the Prentiss Foundation, and the Ritter Foundation; CIHR, the Bebensee Foundation, the C. R. Younger Foundation, the Prentiss Foundation, and the Ritter Foundation had no further role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

Keywords

  • Abnormal Involuntary Movement Scale (AIMS)
  • BDNF
  • DRD3
  • Pharmacogenetics
  • Schizophrenia
  • Tardive dyskinesia

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)

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