Schizophrenia-associated gene dysbindin-1 and tardive dyskinesia

Miriam S. Maes, Justin Y. Lu, Arun K. Tiwari, Natalie Freeman, Vincenzo de Luca, Daniel J. Müller, 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 journalArticle

Abstract

Tardive dyskinesia (TD) is a potentially irreversible movement disorder observed following long-term antipsychotic exposure. Its cause is unknown; however, a genetic component has been supported by studies of affected families. Dysbindin-1, encoded by the dystrobrevin-binding protein 1 DTNBP1 gene, has been associated with schizophrenia and is potentially involved in dopamine neurotransmission through its regulation of dopamine release and dopamine D2 receptor recycling, making it a candidate for investigation in TD. We investigated common variants across the DTNBP1 gene in our schizophrenia/patients with schizoaffective disorder of European ancestry. We found a number of DTNBP1 three-marker haplotypes to be associated with TD occurrence and TD severity (p < 0.05). These preliminary findings, if replicated in larger independent samples, would suggest that drugs targeting dysbindin-1 may be an option in the prevention and treatment of TD.

Original languageEnglish (US)
JournalDrug Development Research
DOIs
StateAccepted/In press - 2020

Keywords

  • dysbindin-1 (DTNBP1)
  • pharmacogenetics
  • schizophrenia
  • tardive dyskinesia (TD)

ASJC Scopus subject areas

  • Drug Discovery

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    Maes, M. S., Lu, J. Y., Tiwari, A. K., Freeman, N., de Luca, V., Müller, D. J., Voineskos, A. N., Potkin, S. G., Lieberman, J. A., Meltzer, H. Y., Remington, G., Kennedy, J. L., & Zai, C. C. (Accepted/In press). Schizophrenia-associated gene dysbindin-1 and tardive dyskinesia. Drug Development Research. https://doi.org/10.1002/ddr.21681