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    Rights statement: This is the peer reviewed version of the following article: Taylor, D. L., Tiwari, A. K., Lieberman, J. A., Potkin, S. G., Meltzer, H. Y., Knight, J., Remington, G., Müller, D. J., and Kennedy, J. L. (2016) Genetic association analysis of N-methyl-d-aspartate receptor subunit gene GRIN2B and clinical response to clozapine. Hum. Psychopharmacol Clin Exp, 31: 121–134. doi: 10.1002/hup.2519 which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/hup.2519/abstract This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.

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Genetic association analysis of N-methyl-d-aspartate receptor subunit gene GRIN2B and clinical response to clozapine

Research output: Contribution to journalJournal articlepeer-review

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  • Danielle L. Taylor
  • Arun K. Tiwari
  • Jeffrey A. Lieberman
  • Steven G. Potkin
  • Herbert Y. Meltzer
  • Jo Knight
  • Gary Remington
  • Daniel J. Müller
  • James L. Kennedy
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<mark>Journal publication date</mark>03/2016
<mark>Journal</mark>Human Psychopharmacology: Clinical and Experimental
Issue number2
Volume31
Number of pages14
Pages (from-to)121-134
Publication StatusPublished
Early online date15/02/16
<mark>Original language</mark>English

Abstract

OBJECTIVE: Approximately 30% of patients with schizophrenia fail to respond to antipsychotic therapy and are classified as having treatment-resistant schizophrenia. Clozapine is the most efficacious drug for treatment-resistant schizophrenia and may deliver superior therapeutic effects partly by modulating glutamate neurotransmission. Response to clozapine is highly variable and may depend on genetic factors as indicated by twin studies. We investigated eight polymorphisms in the N-methyl-d-aspartate glutamate receptor subunit gene GRIN2B with response to clozapine.

METHODS: GRIN2B variants were genotyped using standard TaqMan procedures in 175 European patients with schizophrenia deemed resistant or intolerant to treatment. Response was assessed using change in Brief Psychiatric Rating Scale scores following six months of clozapine therapy. Categorical and continuous response was assessed using chi-squared test and analysis of covariance, respectively.

RESULTS: No associations were observed between the variants and response to clozapine. A-allele carriers of rs1072388 responded marginally better to clozapine therapy than GG-homozygotes; however, the difference was not statistically significant (p = 0.067, uncorrected).

CONCLUSIONS: Our findings do not support a role for these GRIN2B variants in altering response to clozapine in our sample. Investigation of additional glutamate variants in clozapine response is warranted. Copyright © 2016 John Wiley & Sons, Ltd.

Bibliographic note

This is the peer reviewed version of the following article: Taylor, D. L., Tiwari, A. K., Lieberman, J. A., Potkin, S. G., Meltzer, H. Y., Knight, J., Remington, G., Müller, D. J., and Kennedy, J. L. (2016) Genetic association analysis of N-methyl-d-aspartate receptor subunit gene GRIN2B and clinical response to clozapine. Hum. Psychopharmacol Clin Exp, 31: 121–134. doi: 10.1002/hup.2519 which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/hup.2519/abstract This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.