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

• Published in: European journal of clinical pharmacology Vol. 63; no. 3; pp. 233 - 241
• Main Authors: Güzey, Cüneyt, Scordo, Maria Gabriella, Spina, Edoardo, Landsem, Veslemøy Malm, Spigset, Olav
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 01.03.2007; Berlin Springer Nature B.V
• Subjects: Adult; Adult and adolescent clinical studies; Aged; Antipsychotic Agents - adverse effects; Basal Ganglia Diseases - chemically induced; Basal Ganglia Diseases - genetics; Biological and medical sciences; Dopamine Plasma Membrane Transport Proteins - genetics; Dopamine receptors; Dopamine transporter; FARMACI; Female; Genotype; Humans; Male; Medical sciences; Middle Aged; Minisatellite Repeats; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Neurotransmitters; Pharmacology; Pharmacology. Drug treatments; PHARMACY; Polymorphism; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Psychotropic drugs; Receptor, Serotonin, 5-HT2A - genetics; Receptors, Dopamine - genetics; Schizophrenia; Schizophrenia - drug therapy; Serotonin Plasma Membrane Transport Proteins - genetics; Serotonin receptors; Serotonin transporter; Side effects; Human; Nervous system diseases; Genetic variability; Neuroleptic; Psychotropic; Dopamine receptor; Schizophrenia; Genotype; Serotonine receptor; Dopamine receptors Dopamine transporter Serotonin receptors Serotonin transporter; Cerebral disorder; Psychosis; Symptomatology; Serotonin transporter; Central nervous system disease; Antipsychotic; Extrapyramidal syndrome; Polymorphism
• ISSN: 0031-6970; 1432-1041; 1432-1041
• DOI: 10.1007/s00228-006-0234-8

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. 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. 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. 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.