D2 Receptor Genetic Variation and Clinical Response to Antipsychotic Drug Treatment: A Meta-Analysis

• Published in: The American journal of psychiatry 2010-07, Vol.167 (7), p.763-772
• Main Authors: ZHANG, Jian-Ping, LENCZ, Todd, MALHOTRA, Anil K
• Format: Article
• Language: English
• Subjects: Alleles; Antipsychotic Agents - therapeutic use; Biological and medical sciences; Genotype; Humans; Medical sciences; Neuropharmacology; Pharmacology. Drug treatments; Polymorphism, Genetic - genetics; Polymorphism, Single Nucleotide - genetics; Psychiatric Status Rating Scales; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Receptors, Dopamine D2 - genetics; Schizophrenia - drug therapy; Schizophrenia - genetics; Treatment Outcome
• ISSN: 0002-953X; 1535-7228
• DOI: 10.1176/appi.ajp.2009.09040598

Several lines of evidence suggest that antipsychotic drug efficacy is mediated by dopamine type 2 (D(2)) receptor blockade. Therefore, it seems plausible that variation in the DRD(2) gene is associated with clinical response to antipsychotic drug treatment. The authors conducted the first meta-analysis to examine the relationship between DRD2 polymorphisms and antipsychotic drug response. A MEDLINE search of articles available up to December 31, 2008, yielded 18 prospective studies examining DRD2 gene variation and antipsychotic response in schizophrenia patients; of which, 10 independent studies met criteria for inclusion. Clinical response to antipsychotic treatment was defined as a 50% reduction of either the Brief Psychiatric Rating Scale total score or Positive and Negative Syndrome Scale total score at approximately 8 weeks of follow-up evaluation. Odds ratio was the primary effect-size measure and computed for each polymorphism in each study. Sufficient data were available for two DRD2 polymorphisms: -141C Ins/Del and Taq1A. Six studies reported results for the -141C Ins/Del polymorphism (total sample size: N=687). The Del allele carrier was significantly associated with poorer antipsychotic drug response relative to the Ins/Ins genotype. Eight studies assessed the Taq1A polymorphism and antipsychotic response (total sample size: N=748). There was no significant difference in the response rate among A1 allele carriers relative to individuals with the A2/A2 genotype or A2 allele carriers relative to individuals with the A1/A1 genotype. The DRD2 genetic variation is associated with clinical response to antipsychotic drug treatment. These data may provide proof-of-principle for pharmacogenetic studies in schizophrenia.