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

doi:10.1002/ddr.21681

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

Psychiatry and Behavioral Sciences

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

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 language	English (US)
Pages (from-to)	678-684
Number of pages	7
Journal	Drug Development Research
Volume	82
Issue number	5
DOIs	https://doi.org/10.1002/ddr.21681
State	Published - Aug 2021

Funding

We would like to thank the Ministry of Research and Innovation of Ontario, for funding the IMPACT project. We would also like to thank Larry and Judy Tanenbaum for their generous support in creating the Tanenbaum Centre for Pharmacogenetics, which is advancing research for the CAMH Pharmacogenetic Program. Furthermore, we would like to thank the participants in the study.

Keywords

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

ASJC Scopus subject areas

Drug Discovery

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10.1002/ddr.21681

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title = "Schizophrenia-associated gene dysbindin-1 and tardive dyskinesia",

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.",

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year = "2021",

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AU - de Luca, Vincenzo

AU - Müller, Daniel J.

AU - Voineskos, Aristotle N.

AU - Potkin, Steven G.

AU - Lieberman, Jeffrey A.

AU - Meltzer, Herbert Y.

AU - Remington, Gary

AU - Kennedy, James L.

AU - Zai, Clement C.

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Schizophrenia-associated gene dysbindin-1 and tardive dyskinesia

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