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

doi:10.1016/j.euroneuro.2009.01.001

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

Psychiatry and Behavioral Sciences

Research output: Contribution to journal › Article › peer-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 language	English (US)
Pages (from-to)	317-328
Number of pages	12
Journal	European Neuropsychopharmacology
Volume	19
Issue number	5
DOIs	https://doi.org/10.1016/j.euroneuro.2009.01.001
State	Published - 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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10.1016/j.euroneuro.2009.01.001

Cite this

Zai, C. C., Tiwari, A. K., De Luca, V., Müller, D. J., Bulgin, N., Hwang, R., Zai, G. C., King, N., Voineskos, A. N., Meltzer, H. Y., Lieberman, J. A., Potkin, S. G., Remington, G., & Kennedy, J. L. (2009). Genetic study of BDNF, DRD3, and their interaction in tardive dyskinesia. European Neuropsychopharmacology, 19(5), 317-328. https://doi.org/10.1016/j.euroneuro.2009.01.001

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

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.",

keywords = "Abnormal Involuntary Movement Scale (AIMS), BDNF, DRD3, Pharmacogenetics, Schizophrenia, Tardive dyskinesia",

author = "Zai, {Clement C.} and Tiwari, {Arun K.} and {De Luca}, Vincenzo and M{\"u}ller, {Daniel J.} and Natalie Bulgin and Rudi Hwang and Zai, {Gwyneth C.} and Nicole King and Voineskos, {Aristotle N.} and Meltzer, {Herbert Y.} and Lieberman, {Jeffrey A.} and Potkin, {Steven G.} and Gary Remington and Kennedy, {James L.}",

note = "Funding Information: 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. ",

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doi = "10.1016/j.euroneuro.2009.01.001",

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T1 - Genetic study of BDNF, DRD3, and their interaction in tardive dyskinesia

AU - Zai, Clement C.

AU - Tiwari, Arun K.

AU - De Luca, Vincenzo

AU - Müller, Daniel J.

AU - Bulgin, Natalie

AU - Hwang, Rudi

AU - Zai, Gwyneth C.

AU - King, Nicole

AU - Voineskos, Aristotle N.

AU - Meltzer, Herbert Y.

AU - Lieberman, Jeffrey A.

AU - Potkin, Steven G.

AU - Remington, Gary

AU - Kennedy, James L.

N1 - Funding Information: 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.

PY - 2009/5

Y1 - 2009/5

N2 - 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.

AB - 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.

KW - Abnormal Involuntary Movement Scale (AIMS)

KW - BDNF

KW - DRD3

KW - Pharmacogenetics

KW - Schizophrenia

KW - Tardive dyskinesia

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SN - 0924-977X

VL - 19

SP - 317

EP - 328

JO - European Neuropsychopharmacology

JF - European Neuropsychopharmacology

IS - 5

ER -

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

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