DRD2 promoter region variation as a predictor of sustained response to antipsychotic medication in first-episode schizophrenia patients.
OBJECTIVE
All antipsychotics act on the dopamine D(2) receptor. The present study extends prior pharmacogenetic investigations of the D(2) receptor gene (DRD2) by examining, in first-episode schizophrenia patients, promoter region variation as a predictor of response time to two first-line atypical antipsychotics.


METHODS
Patients experiencing their first episode of schizophrenia (N=61) were genotyped for two DRD2 promoter region polymorphisms (A-241G and -141C Ins/Del) and were randomly assigned to receive 16 weeks of treatment with either risperidone or olanzapine. Time until sustained response (two consecutive ratings without significant positive symptoms) for rare allele carriers versus wild types was examined by using Kaplan-Meier curves.


RESULTS
Relative to wild type homozygotes, G carriers (A-241G) exhibited a significantly faster time until response, whereas -141C Del carriers took a significantly longer time to respond. Diplotype analysis revealed similar results.


CONCLUSIONS
These findings suggest that variation in the D(2) receptor gene can, in part, explain variation in the timing of clinical response to antipsychotics in patients with first-episode schizophrenia.
Lencz
Todd
T
Department of Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, NY 11004, USA. lencz@lij.edu
Robinson
Delbert G
DG
Xu
Ke
K
Ekholm
Jenny
J
Sevy
Serge
S
Gunduz-Bruce
Handan
H
Woerner
Margaret G
MG
Kane
John M
JM
Goldman
David
D
Malhotra
Anil K
AK
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D000077152:Olanzapine; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D018967:Risperidone / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics*; D012565:Schizophrenic Psychology; D013997:Time Factors; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; D001569:Benzodiazepines; D018967:Risperidone; D000077152:Olanzapine