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

作者：Guzey Cuneyt^*; Scordo Maria Gabriella; Spina Edoardo; Landsem Veslemoy Malm; Spigset Olav

来源：European Journal of Clinical Pharmacology, 2007, 63(3): 233-241.

DOI：10.1007/s00228-006-0234-8

• dopamine receptors
• dopamine transporter
• serotonin receptors
• serotonin transporter
• polymorphism

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 D-2 receptor (DRD2) gene, the Msc1 polymorphism of the dopamine D-3 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.

• 出版日期2007-3