Journal
HUMAN PSYCHOPHARMACOLOGY-CLINICAL AND EXPERIMENTAL
Volume 31, Issue 2, Pages 121-134Publisher
WILEY
DOI: 10.1002/hup.2519
Keywords
GRIN2B; pharmacogenetics; clozapine; glutamate; schizophrenia
Funding
- Canadian Institutes for Health Research (CIHR) [MOP 15007, 200508GMH, MOP 89853]
- NARSAD Young Investigator Award
- Early Researcher Award by the Ministry of Research and Innovation of Ontario
- CIHR Michael Smith New Investigator Salary Prize for Research in Schizophrenia
- OMHF New Investigator Fellowship
- CAMH postdoctoral fellowship
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ObjectiveApproximately 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. MethodsGRIN2B 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. ResultsNo 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). ConclusionsOur 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 (c) 2016 John Wiley & Sons, Ltd.
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