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Schizophr Res. 2013 May;146(1-3):285-8. doi: 10.1016/j.schres.2013.01.020. Epub 2013 Feb 19.

Genetic variation in BDNF is associated with antipsychotic treatment resistance in patients with schizophrenia.

Author information

  • 1Department of Psychiatry, Zucker Hillside Hospital, North Shore-Long Island Jewish Health System, Glen Oaks, NY 11004, United States. jzhang1@nshs.edu

Abstract

OBJECTIVE:

Antipsychotic drugs are the mainstay of treatment for schizophrenia. However, a substantial proportion of patients are poorly responsive or resistant to first-line treatments, and clozapine treatment is often indicated. Therefore, we and others have used clozapine treatment as a proxy phenotype for antipsychotic treatment resistance in pharmacogenetic studies. In the present study, we utilized this phenotype to test previously-identified candidate genes for antipsychotic treatment response.

METHOD:

We assessed 89 Caucasian schizophrenia patients clinically assigned to clozapine treatment versus 190 Caucasian patients that were not selected for clozapine treatment. We conducted gene-based association tests on a set of 74 relevant candidate genes nominated in the CATIE pharmacogenetic study (Need et al., 2009), using the GATES procedure (Li et al., 2011).

RESULTS:

After correcting for multiple testing in the gene-based association test, the gene for brain derived neurotrophic factor (BDNF) was significantly associated with treatment resistance. The top single nucleotide polymorphisms (SNPs) in BDNF included rs11030104 (OR = 2.57), rs10501087 (OR = 2.19) and rs6265 (Val66Met) (OR = 2.08). These SNPs appear to be in high linkage disequilibrium with each other.

CONCLUSION:

BDNF appears to have a strong association with antipsychotic treatment resistance. Future studies are needed to replicate this finding and further elucidate the biological pathways underlying the association between BDNF and antipsychotic drug response.

Copyright © 2013 Elsevier B.V. All rights reserved.

PMID:
23433505
[PubMed - indexed for MEDLINE]
PMCID:
PMC3622803
Free PMC Article
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