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Association between the serotonin 2A receptor gene and tardive dyskinesia in chronic schizophrenia

Molecular Psychiatry volume 6, pages 225–229 (2001)Cite this article

Abstract

Tardive dyskinesia (TD) is a long-term adverse effect of antipsychotic drugs that are dopamine D2 receptor blockers.1 Serotonin receptor antagonism has been proposed as a common mechanism contributing to the low extrapyramidal effects profile of atypical antipsychotic drugs.2 We examined the association of three polymorphisms in the 5-HT2A receptor gene (HTR2A) with TD susceptibility—T102C3 and his452tyr4 in the coding region and A-1438G5 in the promoter—in matched schizophrenia patients with (n = 59, SCZ-TD-Y) and without TD (n = 62, SCZ-TD-N) and normal control subjects (n = 96). The T102C and the A-1438G polymorphisms are in complete linkage disequilibrium but not his452tyr. There was a significant excess of 102C and −1438G alleles (62.7%) in the SCZ-TD-Y patients compared to SCZ-TD-N patients (41.1%) and controls (45.9%; χ2 = 12.8, df = 2, P = 0.002; SCZ-TD-Y vs SCZ-TD-N, χ2 = 11.4, df = 1, P = 0.0008, OR 2.41, 95% CI 1.43–3.99) and of 102CC and −1438GG genotypes (SCZ-TD-Y 42.4%, SCZ-TD-N, 16.1%, controls 20.8%, χ2 = 13.3, df = 4, P = 0.01). The 102CC and the −1438GG genotypes were associated with significantly higher AIMS trunk dyskinesia scores (F = 3.9; df = 2, 116; P = 0.02) and more incapacitation (F = 5.0; df = 2, 115; P = 0.006). The his452tyr polymorphism showed no association with TD. These findings suggest that the 5-HT2A receptor gene is significantly associated with susceptibility to TD in patients with chronic schizophrenia. Previously reported association of the T102C and A-1438G polymorphisms with schizophrenia6 may reflect association of a sub-group of patients with a susceptibility to abnormal involuntary movements related to antipsychotic drug exposure.

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Acknowledgements

This work was supported in part by grants from the Yisumi Fund of Hadassit Research and Development Corporation and the National Institute for Psychobiology in Israel (to RS) and the India–Israel Human Genome Collaboration (to BL). The Biological Psychiatry Laboratory, Hadassah–Hebrew University Medical Center (http://www.hadassah.org.il/departments/biopsyc/), 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 & 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. Talbieh Hospital, Jerusalem, Israel

    A Dorevitch

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  1. R H Segman
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Correspondence to R H Segman or B Lerer.

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Segman, R., Heresco-Levy, U., Finkel, B. et al. Association between the serotonin 2A receptor gene and tardive dyskinesia in chronic schizophrenia. Mol Psychiatry 6, 225–229 (2001). https://doi.org/10.1038/sj.mp.4000842

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