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Association of dopaminergic and serotonergic genes with tardive dyskinesia in patients with chronic schizophrenia

The Pharmacogenomics Journal volume 3, pages 277–283 (2003)Cite this article

ABSTRACT

Tardive dyskinesia (TD) is a long-term adverse effect of antipsychotic drugs that are dopamine D2 receptor blockers. Serotonin receptor antagonism has been proposed as a common mechanism contributing to the low extrapyramidal side effect profile of atypical antipsychotic drugs. We evaluated candidate dopamine and serotonin genes for association with drug-induced TD. We examined three polymorphisms in the dopamine D2 receptor gene (DRD2), two sites in the 3′ region of the dopamine transporter (DAT) gene, two sites in the promoter and coding region of the dopamine D4 (DRD4) receptor gene, as well as polymorphic sites in the serotonin 6 receptor gene, the serotonin transporter gene and the tryptophan hydroxylase gene, for association with TD susceptibility. Schizophrenic patients with (n=59) and without TD (n=63), matched for antipsychotic drug exposure and other relevant variables, were studied. No significant associations were found. Within the limitations imposed by the size of the clinical sample, these findings suggest that the above polymorphic loci do not contribute significantly to risk for TD. Further examination of loci that yielded positive results at a trend level and investigation of other candidate genetic loci coding for antipsychotic drug targets is warranted.

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Acknowledgements

This work was supported in part by grants from the Yisumi Fund of Hadassit Research and Development Corporation the NARSAD young investigator award and the National Institute for Psychobiology in Israel to RHS and the India–Israel Human Genome Research Project to BL, The Biological Psychiatry Laboratory, Hadassah Hebrew University Medical Center, is supported by the Harry Stern Family Foundation.

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Authors and Affiliations

  1. Department of Psychiatry, Biological Psychiatry Laboratory, Hadassah Hebrew University Medical Center, Jerusalem, Israel

    R H Segman, T Goltser, R Shalem, A Yakir, A Shelevoy & B Lerer

  2. Herzog Hospital, Jerusalem, Israel

    U Heresco-Levy & D Greenberg

  3. Lev Hasharon Hospital, Pardessia, Israel

    B Finkel & A Lerner

  4. Kfar Shaul Hospital, Jerusalem, Israel

    M Schlafman

  5. Beer Yaakov Mental Health Center,

    R Strous

  6. Israel

    R Strous

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  1. R H Segman
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Correspondence to R H Segman.

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Segman, R., Goltser, T., Heresco-Levy, U. et al. Association of dopaminergic and serotonergic genes with tardive dyskinesia in patients with chronic schizophrenia. Pharmacogenomics J 3, 277–283 (2003). https://doi.org/10.1038/sj.tpj.6500194

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