Further evidence for the association between 5-HT2C receptor gene polymorphisms and extrapyramidal side effects in male schizophrenic patients.
BACKGROUND
Antipsychotic-induced extrapyramidal side effects (EPS) are still a major problem in the treatment of schizophrenia. Serotonin 2C receptors (5-HT(2C)) have regulatory effects on dopaminergic pathways in brain regions involved with EPS. Polymorphisms in the 5-HT(2C) gene (HTR2C) have been suggested to be associated with the risk of developing EPS.


OBJECTIVE
Our purpose was to evaluate the impact of polymorphisms in the HTR2C gene on the occurrence of EPS in male schizophrenic patients.


METHODS
Ninety-nine male Caucasian chronic schizophrenic patients on long-term treatment with classical antipsychotics were genotyped for the -997 G/A, -759 C/T, -697 G/C and Cys23Ser polymorphisms of HTR2C. EPS (dystonia, parkinsonism, tardive dyskinesia) were assessed by the Simpson-Angus Scale and the Abnormal Involuntary Movement Scale. Fifty-one patients had current or previous history of EPS, whereas 48 patients had no symptoms or history of EPS. To rule out a possible association between HTR2C polymorphisms and schizophrenia, 112 healthy male volunteers were also genotyped.


RESULTS
Allele frequencies of -997A, -759T and -697C did not differ between the groups, whereas patients with EPS had a significantly (p = 0.025) higher frequency of the 23Ser allele (0.29) than did patients without EPS (0.15) or healthy volunteers (0.13). A similar trend was observed for a haplotype including the -997G, -759C, -697C and 23Ser alleles (p = 0.04).


CONCLUSIONS
Results confirm previously reported associations between the HTR2C 23Ser allele and EPS occurrence and suggest the novel finding of an HTR2C haplotype association with EPS in male chronic schizophrenic patients.
Gunes
Arzu
A
Department of Medical Sciences, Clinical Pharmacology, Uppsala University Hospital, SE-75185, Uppsala, Sweden.
Dahl
Marja-Liisa
ML
Spina
Edoardo
E
Scordo
Maria Gabriella
MG
D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001480:Basal Ganglia Diseases / Q000139:chemically induced* / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy*
D014150:Antipsychotic Agents; D044405:Receptor, Serotonin, 5-HT2C