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Antipsychotic-induced extrapyramidal symptoms in patients with schizophrenia: associations with dopamine and serotonin receptor and transporter polymorphisms

  • Pharmacodynamics
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Abstract

Background

Little is known about the influence of polymorphisms of the dopamine and serotonin system on the risk for extrapyramidal symptoms (EPS) during treatment with antipsychotic drugs.

Methods

Of 119 subjects with schizophrenia treated with antipsychotics, 63 had current or previous EPS (acute dystonia, parkinsonism, tardive dyskinesia), and 56 had no such symptoms. All subjects were genotyped for a total of eight dopamine and serotonin receptor and transporter polymorphisms: the Taq1A polymorphism of the dopamine D2 receptor (DRD2) gene, the Msc1 polymorphism of the dopamine D3 receptor (DRD3) gene, the variable number of tandem repeat (VNTR) polymorphism of the dopamine transporter (DAT1) gene, four polymorphisms (102T/C, His452Tyr, 516 C/T, and Thr25Asn) of the serotonin 5-HT2A receptor (5HTR2A) gene, and the 5HTTLPR polymorphism of the serotonin transporter (5HTT) gene.

Results

The frequency of the A1 allele of the DRD2 Taq1A polymorphism was significantly higher in the EPS group than in the control group [16% vs. 7%, P = 0.040; odds ratio (OR) 2.4; 95% confidence interval (CI) 1.1–5.7]. Also, the 9 repeat allele of the DAT1 VNTR polymorphism was significantly more common in the EPS group (42% vs. 28%, P = 0.030; OR 1.9; 95% CI 1.1–3.3). Being a carrier of both DRD2 Taq1A A1 and DAT1 VNTR 9 repeat alleles was also significantly associated with the occurrence of EPS (19% vs. 6%, P = 0.040; OR 4.0; 95% CI 1.05–15.2) No significant differences in allele frequencies were found for the other polymorphisms.

Conclusion

Presence of the Taq1A A1 allele of the DRD2 and the 9 repeat allele of the DAT1 VNTR polymorphisms might be risk factors for EPS caused by antipsychotic drugs.

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Acknowledgements

We acknowledge Trine Nordgård Løkken and Torill Fladvad for excellent technical assistance.

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Authors and Affiliations

  1. Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway

    Cüneyt Güzey & Olav Spigset

  2. Department of Laboratory Medicine, Children’s and Women’s Health, Norwegian University of Science and Technology, Trondheim, Norway

    Cüneyt Güzey, Veslemøy Malm Landsem & Olav Spigset

  3. Department of Medical Sciences, Clinical Pharmacology, Uppsala University, Uppsala, Sweden

    Maria Gabriella Scordo

  4. Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Italy and IRCCS Centro Neurolesi “Bonino-Pulejo”, Messina, Italy

    Edoardo Spina

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  1. Cüneyt Güzey
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  2. Maria Gabriella Scordo
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Correspondence to Cüneyt Güzey.

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Güzey, C., Scordo, M.G., Spina, E. et al. Antipsychotic-induced extrapyramidal symptoms in patients with schizophrenia: associations with dopamine and serotonin receptor and transporter polymorphisms. Eur J Clin Pharmacol 63, 233–241 (2007). https://doi.org/10.1007/s00228-006-0234-8

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