title: Genetic variation in BDNF is associated with antipsychotic treatment resistance in patients with schizophrenia.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Psychiatry, Zucker Hillside Hospital, North Shore-Long Island Jewish Health System, Glen Oaks, NY 11004, United States. jzhang1@nshs.edu
authors: Jian-Ping
authors: JP
authors: Zhang
authors: Todd
authors: T
authors: Lencz
authors: Stephen
authors: S
authors: Geisler
authors: Pamela
authors: P
authors: DeRosse
authors: Evelyn J
authors: EJ
authors: Bromet
authors: Anil K
authors: AK
authors: Malhotra
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003024:Clozapine / Q000009:adverse effects*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics*
chemical_list: D014150:Antipsychotic Agents; D019208:Brain-Derived Neurotrophic Factor; D003024:Clozapine