Serotonin and dopamine receptor gene polymorphisms and the risk of extrapyramidal side effects in perphenazine-treated schizophrenic patients.
BACKGROUND
Perphenazine, a classical antipsychotic drug, has the potential to induce extrapyramidal side effects (EPS). Dopaminergic and serotonergic pathways are involved in the therapeutic and adverse effects of the drug.


OBJECTIVE
To evaluate the impact of polymorphisms in the dopamine D(2) and D(3) and serotonin 2A and 2C receptor genes (DRD2, DRD3, HTR2A, and HTR2C) on short-term effects of perphenazine monotherapy in schizophrenic patients.


METHODS
Forty-seven Estonian inpatients were evaluated before and after 4-6 weeks of treatment by Simpson-Angus rating scale, Barnes scale, and Positive and Negative Symptom Scale. Genotyping was performed for common DRD2, DRD3, HTR2A, and HTR2C gene polymorphisms, previously reported to influence receptor expression and/or function.


RESULTS
Most of the patients (n = 37) responded to the treatment and no significant association was observed between the polymorphisms and antipsychotic response. The 102C allele of HTR2A and the -697C and 23Ser alleles of HTR2C were more frequent among patients with EPS (n = 25) compared to patients without EPS (n = 22) (p = 0.02, 0.01, and 0.02, respectively). The difference between patients with and without EPS in variant allele frequencies remained significant after multiple model analyses including age, gender, and duration of antipsychotic treatment as covariants. There was no significant association between EPS occurrence and polymorphisms in the DRD2 and DRD3 genes.


CONCLUSIONS
An association was observed between polymorphisms in HTR2A and HTR2C genes and occurrence of acute EPS in schizophrenic patients treated with perphenazine monotherapy. Larger study populations are needed to confirm our findings.
Gunes
Arzu
A
Department of Medical Sciences, Clinical Pharmacology, Uppsala University Hospital, 75185, Uppsala, Sweden.
Scordo
Maria Gabriella
MG
Jaanson
Peeter
P
Dahl
Marja-Liisa
ML
D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects*; D018492:Dopamine Antagonists / Q000009:adverse effects*; D004409:Dyskinesia, Drug-Induced / Q000209:etiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010546:Perphenazine / Q000009:adverse effects*; D011110:Polymorphism, Genetic; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics; D011954:Receptors, Dopamine / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics; D050637:Receptors, Dopamine D3 / Q000235:genetics; D011985:Receptors, Serotonin / Q000235:genetics*; D012307:Risk Factors; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics; D013997:Time Factors; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D011985:Receptors, Serotonin; D010546:Perphenazine