PMID- 23433505
OWN - NLM
STAT- MEDLINE
DCOM- 20131025
LR  - 20220330
IS  - 1573-2509 (Electronic)
IS  - 0920-9964 (Print)
IS  - 0920-9964 (Linking)
VI  - 146
IP  - 1-3
DP  - 2013 May
TI  - Genetic variation in BDNF is associated with antipsychotic treatment resistance 
      in patients with schizophrenia.
PG  - 285-8
LID - S0920-9964(13)00058-3 [pii]
LID - 10.1016/j.schres.2013.01.020 [doi]
AB  - 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.
CI  - Copyright (c) 2013 Elsevier B.V. All rights reserved.
FAU - Zhang, Jian-Ping
AU  - Zhang JP
AD  - Department of Psychiatry, Zucker Hillside Hospital, North Shore-Long Island 
      Jewish Health System, Glen Oaks, NY 11004, United States. jzhang1@nshs.edu
FAU - Lencz, Todd
AU  - Lencz T
FAU - Geisler, Stephen
AU  - Geisler S
FAU - DeRosse, Pamela
AU  - DeRosse P
FAU - Bromet, Evelyn J
AU  - Bromet EJ
FAU - Malhotra, Anil K
AU  - Malhotra AK
LA  - eng
GR  - K23 MH001760/MH/NIMH NIH HHS/United States
GR  - MH065580/MH/NIMH NIH HHS/United States
GR  - K01 MH065580/MH/NIMH NIH HHS/United States
GR  - P50MH080173/MH/NIMH NIH HHS/United States
GR  - K23 MH097108/MH/NIMH NIH HHS/United States
GR  - MH001760/MH/NIMH NIH HHS/United States
GR  - P50 MH080173/MH/NIMH NIH HHS/United States
GR  - P30 MH090590/MH/NIMH NIH HHS/United States
GR  - 1K23MH097108/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130219
PL  - Netherlands
TA  - Schizophr Res
JT  - Schizophrenia research
JID - 8804207
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - J60AR2IKIC (Clozapine)
SB  - IM
MH  - Adult
MH  - Antipsychotic Agents/*adverse effects
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Clozapine/*adverse effects
MH  - Female
MH  - Genetic Association Studies
MH  - Humans
MH  - Linkage Disequilibrium
MH  - Male
MH  - Middle Aged
MH  - *Pharmacogenetics
MH  - Polymorphism, Single Nucleotide/*genetics
MH  - Schizophrenia/drug therapy/*genetics
PMC - PMC3622803
MID - NIHMS439304
EDAT- 2013/02/26 06:00
MHDA- 2013/10/26 06:00
PMCR- 2014/05/01
CRDT- 2013/02/26 06:00
PHST- 2012/10/16 00:00 [received]
PHST- 2013/01/04 00:00 [revised]
PHST- 2013/01/07 00:00 [accepted]
PHST- 2013/02/26 06:00 [entrez]
PHST- 2013/02/26 06:00 [pubmed]
PHST- 2013/10/26 06:00 [medline]
PHST- 2014/05/01 00:00 [pmc-release]
AID - S0920-9964(13)00058-3 [pii]
AID - 10.1016/j.schres.2013.01.020 [doi]
PST - ppublish
SO  - Schizophr Res. 2013 May;146(1-3):285-8. doi: 10.1016/j.schres.2013.01.020. Epub 
      2013 Feb 19.