PMID- 27546373
OWN - NLM
STAT- MEDLINE
DCOM- 20180129
LR  - 20210816
IS  - 1873-7862 (Electronic)
IS  - 0924-977X (Linking)
VI  - 26
IP  - 10
DP  - 2016 Oct
TI  - Pharmacogenetic study of the effects of raloxifene on negative symptoms of 
      postmenopausal women with schizophrenia: A double-blind, randomized, 
      placebo-controlled trial.
PG  - 1683-9
LID - S0924-977X(16)30163-8 [pii]
LID - 10.1016/j.euroneuro.2016.08.006 [doi]
AB  - Several double-blind clinical trials have reported improvement in positive, 
      negative and cognitive symptoms of schizophrenia with raloxifene, a selective 
      receptor estrogen modulator. However, there are some inconsistencies in 
      replicating findings between studies of different countries. The failure to 
      replicate these findings may result from genetic factors that could explain some 
      of the variability in the treatment response. However, pharmacogenetic studies 
      exploring this topic in women with schizophrenia are lacking. We aimed to conduct 
      an exploratory pharmacogenetic analysis of a double-blind, randomized, parallel, 
      placebo-controlled study of 24 weeks' duration of raloxifene aiming to improve 
      negative symptoms in postmenopausal women with schizophrenia. Four single 
      nucleotide polymorphisms (SNPs) were studied: rs9340799, rs2234693 and rs1801132 
      in the Estrogen Receptor 1 (ESR1) gene, and rs1042597 in the 
      UDP-glucuronosyltransferase 1A8 (UGT1A8) gene. Sixty-five postmenopausal women 
      with schizophrenia (DSM-IV) were randomized to either 60mg/day adjunctive 
      raloxifene (36 women) or adjunctive placebo (29 women). Psychopathological 
      symptoms were assessed at baseline and at weeks 4, 12, and 24 with the Positive 
      and Negative Syndrome Scale (PANSS). Of the four studied SNPs, the rs1042597 
      variant in the UGT1A8 gene was associated with a different treatment response in 
      negative symptoms with raloxifene treatment, whereas the rs2234693 variant in the 
      ESR1 gene was associated with a distinct response in general psychopathology. In 
      conclusion, our study suggests that genetic variants in UGT1A8 and ESR1 genes 
      modulate the treatment response to adding raloxifene to antipsychotic treatment 
      in postmenopausal women with schizophrenia.
CI  - Copyright (c) 2016 Elsevier B.V. and ECNP. All rights reserved.
FAU - Labad, Javier
AU  - Labad J
AD  - Corporacio Sanitaria i Universitaria Parc Tauli, Mental Health Department, 
      Universitat Autonoma de Barcelona, Sabadell, Spain; Catalan Group in Women's 
      Mental Health Research (GTRDSM), Barcelona, Spain; Instituto de Salud Carlos III, 
      Centro de Investigacion en Red de Salud Mental (CIBERSAM), Madrid, Spain. 
      Electronic address: jlabad@tauli.cat.
FAU - Martorell, Lourdes
AU  - Martorell L
AD  - Hospital Universitari Institut Pere Mata, IISPV, Universitat Rovira i Virgili, 
      Reus, Spain; Instituto de Salud Carlos III, Centro de Investigacion en Red de 
      Salud Mental (CIBERSAM), Madrid, Spain.
FAU - Huerta-Ramos, Elena
AU  - Huerta-Ramos E
AD  - Catalan Group in Women's Mental Health Research (GTRDSM), Barcelona, Spain; 
      Instituto de Salud Carlos III, Centro de Investigacion en Red de Salud Mental 
      (CIBERSAM), Madrid, Spain; Parc Sanitari Sant Joan de Deu, Research and 
      Development Unit, Sant Boi de Llobregat, Spain.
FAU - Cobo, Jesus
AU  - Cobo J
AD  - Corporacio Sanitaria i Universitaria Parc Tauli, Mental Health Department, 
      Universitat Autonoma de Barcelona, Sabadell, Spain; Catalan Group in Women's 
      Mental Health Research (GTRDSM), Barcelona, Spain; Instituto de Salud Carlos III, 
      Centro de Investigacion en Red de Salud Mental (CIBERSAM), Madrid, Spain.
FAU - Vilella, Elisabet
AU  - Vilella E
AD  - Hospital Universitari Institut Pere Mata, IISPV, Universitat Rovira i Virgili, 
      Reus, Spain; Instituto de Salud Carlos III, Centro de Investigacion en Red de 
      Salud Mental (CIBERSAM), Madrid, Spain.
FAU - Rubio-Abadal, Elena
AU  - Rubio-Abadal E
AD  - Catalan Group in Women's Mental Health Research (GTRDSM), Barcelona, Spain; 
      Instituto de Salud Carlos III, Centro de Investigacion en Red de Salud Mental 
      (CIBERSAM), Madrid, Spain; Parc Sanitari Sant Joan de Deu, Research and 
      Development Unit, Sant Boi de Llobregat, Spain.
FAU - Garcia-Pares, Gemma
AU  - Garcia-Pares G
AD  - Catalan Group in Women's Mental Health Research (GTRDSM), Barcelona, Spain; Cap 
      EAE Salut Mental, Andorra.
FAU - Creus, Marta
AU  - Creus M
AD  - Hospital Universitari Institut Pere Mata, IISPV, Universitat Rovira i Virgili, 
      Reus, Spain.
FAU - Nunez, Cristian
AU  - Nunez C
AD  - Instituto de Salud Carlos III, Centro de Investigacion en Red de Salud Mental 
      (CIBERSAM), Madrid, Spain; Parc Sanitari Sant Joan de Deu, Research and 
      Development Unit, Sant Boi de Llobregat, Spain.
FAU - Ortega, Laura
AU  - Ortega L
AD  - Hospital Universitari Institut Pere Mata, IISPV, Universitat Rovira i Virgili, 
      Reus, Spain; Instituto de Salud Carlos III, Centro de Investigacion en Red de 
      Salud Mental (CIBERSAM), Madrid, Spain.
FAU - Miquel, Eva
AU  - Miquel E
AD  - Instituto de Salud Carlos III, Centro de Investigacion en Red de Salud Mental 
      (CIBERSAM), Madrid, Spain; Parc Sanitari Sant Joan de Deu, Research and 
      Development Unit, Sant Boi de Llobregat, Spain.
CN  - RALOPSYCAT Group
FAU - Usall, Judith
AU  - Usall J
AD  - Catalan Group in Women's Mental Health Research (GTRDSM), Barcelona, Spain; 
      Instituto de Salud Carlos III, Centro de Investigacion en Red de Salud Mental 
      (CIBERSAM), Madrid, Spain; Parc Sanitari Sant Joan de Deu, Research and 
      Development Unit, Sant Boi de Llobregat, Spain.
LA  - eng
PT  - Journal Article
DEP - 20160818
PL  - Netherlands
TA  - Eur Neuropsychopharmacol
JT  - European neuropsychopharmacology : the journal of the European College of 
      Neuropsychopharmacology
JID - 9111390
RN  - 0 (ESR1 protein, human)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Selective Estrogen Receptor Modulators)
RN  - 4F86W47BR6 (Raloxifene Hydrochloride)
RN  - EC 2.4.1.17 (Glucuronosyltransferase)
RN  - EC 2.4.1.17 (UDP-glucuronosyltransferase, UGT1A8)
SB  - IM
MH  - Age of Onset
MH  - Aged
MH  - Diagnostic and Statistical Manual of Mental Disorders
MH  - Double-Blind Method
MH  - Estrogen Receptor alpha/genetics
MH  - Female
MH  - Genotype
MH  - Glucuronosyltransferase/genetics
MH  - Humans
MH  - Middle Aged
MH  - *Pharmacogenetics
MH  - Pharmacogenomic Testing
MH  - Polymorphism, Single Nucleotide/genetics
MH  - Postmenopause/psychology
MH  - Raloxifene Hydrochloride/*adverse effects
MH  - *Schizophrenia
MH  - *Schizophrenic Psychology
MH  - Selective Estrogen Receptor Modulators/*adverse effects
OTO - NOTNLM
OT  - Genetics
OT  - Negative symptoms
OT  - Pharmacogenetics
OT  - Postmenopause
OT  - Raloxifene
OT  - Schizophrenia
EDAT- 2016/08/23 06:00
MHDA- 2018/01/30 06:00
CRDT- 2016/08/23 06:00
PHST- 2016/03/16 00:00 [received]
PHST- 2016/07/20 00:00 [revised]
PHST- 2016/08/05 00:00 [accepted]
PHST- 2016/08/23 06:00 [entrez]
PHST- 2016/08/23 06:00 [pubmed]
PHST- 2018/01/30 06:00 [medline]
AID - S0924-977X(16)30163-8 [pii]
AID - 10.1016/j.euroneuro.2016.08.006 [doi]
PST - ppublish
SO  - Eur Neuropsychopharmacol. 2016 Oct;26(10):1683-9. doi: 
      10.1016/j.euroneuro.2016.08.006. Epub 2016 Aug 18.