Antipsychotic-induced extrapyramidal symptoms in patients with schizophrenia: associations with dopamine and serotonin receptor and transporter polymorphisms.
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-HT(2A) 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.


CONCLUSIONS
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.
Güzey
Cüneyt
C
Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway. ismail.c.guzey@legemidler.no
Scordo
Maria Gabriella
MG
Spina
Edoardo
E
Landsem
Veslemøy Malm
VM
Spigset
Olav
O
D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001480:Basal Ganglia Diseases / Q000139:chemically induced* / Q000235:genetics; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics*; D011954:Receptors, Dopamine / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
D014150:Antipsychotic Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D044402:Receptor, Serotonin, 5-HT2A; D011954:Receptors, Dopamine; C493214:SLC6A3 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins