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Further evidence for the association between 5-HT2C receptor gene polymorphisms and extrapyramidal side effects in male schizophrenic patients

  • Pharmacogenetics
  • Published:
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Abstract

Rationale

Antipsychotic-induced extrapyramidal side effects (EPS) are still a major problem in the treatment of schizophrenia. Serotonin 2C receptors (5-HT2C) have regulatory effects on dopaminergic pathways in brain regions involved with EPS. Polymorphisms in the 5-HT2C 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.

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Acknowledgements

This study was supported by grants from the Swedish Research Council, the Swedish Society of Medicine, Svenska Lundbeckstiftelsen, and Fredrik och Ingrid Thurings Stiftelse. Niclas Eriksson, MSc, Uppsala Clinical Research Center, is gratefully acknowledged for assistance in statistical analysis. The study was performed in accordance with the laws of the countries in which it was performed.

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Authors and Affiliations

  1. Department of Medical Sciences, Clinical Pharmacology, Uppsala University Hospital, SE-75185, Uppsala, Sweden

    Arzu Gunes, Marja-Liisa Dahl & Maria Gabriella Scordo

  2. Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Messina, Italy

    Edoardo Spina

  3. IRCCS Centro Neurolesi “Bonino-Pulejo”, Messina, Italy

    Edoardo Spina

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  1. Arzu Gunes
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  2. Marja-Liisa Dahl
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  4. Maria Gabriella Scordo
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Correspondence to Maria Gabriella Scordo.

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Gunes, A., Dahl, ML., Spina, E. et al. Further evidence for the association between 5-HT2C receptor gene polymorphisms and extrapyramidal side effects in male schizophrenic patients. Eur J Clin Pharmacol 64, 477–482 (2008). https://doi.org/10.1007/s00228-007-0450-x

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  • DOI: https://doi.org/10.1007/s00228-007-0450-x

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