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Published Online: 1 July 2010

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

Abstract

Objective

Several lines of evidence suggest that antipsychotic drug efficacy is mediated by dopamine type 2 (D2) receptor blockade. Therefore, it seems plausible that variation in the DRD2 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.

Method

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.

Results

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.

Conclusions

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.

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Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 763 - 772
PubMed: 20194480

History

Received: 30 April 2009
Accepted: 8 October 2009
Published online: 1 July 2010
Published in print: July 2010

Authors

Details

Jian-Ping Zhang, M.D., Ph.D.
Anil K. Malhotra, M.D.

Notes

Received April 30, 2009; revisions received July 24 and August 28, 2009; accepted Oct. 8, 2009. From the Division of Psychiatry Research, Zucker Hillside Hospital, Feinstein Institute of Medical Research, North Shore-Long Island Jewish Health System, Glen Oaks, New York. Address correspondence and reprint requests to Dr. Zhang, Division of Psychiatry Research, Department of Psychiatry, The Zucker Hillside Hospital, 75-59 263rd St., Glen Oaks, NY 11004; [email protected] (e-mail).

Competing Interests

Dr. Lencz is a consultant for Eli Lilly. Dr. Malhotra is a consultant/advisor for Eli Lilly, Janssen, Vanda, and Wyeth; he also serves on the speaker's bureau of Bristol-Myers Squibb. Dr. Zhang reports no financial relationships with commercial interests.

Funding Information

Supported in part by National Institute of Mental Health grants 1P30MH-074543 (principal investigator, J. Kane, M.D.), 1P50MH-080173 (principal investigator, J. Kane, M.D.), 1R01MH-79800-01 (Dr. Malhotra), and K01MH65580 (Dr. Lencz).

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