Psychopharmacology

, Volume 152, Issue 4, pp 408–413

Association between the serotonin 2C receptor gene and tardive dyskinesia in chronic schizophrenia: additive contribution of 5-HT2Cser and DRD3gly alleles to susceptibility

Authors

  • Ronnen H. Segman
    • Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah – Hebrew University Medical Center, Ein Karem, Jerusalem 91120, Israel
  • Uriel Heresco-Levy
    • Herzog Hospital, Jerusalem, Israel
  • Boris Finkel
    • Lev Hasharon Hospital, Pardessia, Israel
  • Roi Inbar
    • Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah – Hebrew University Medical Center, Ein Karem, Jerusalem 91120, Israel
  • Tal Neeman
    • Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah – Hebrew University Medical Center, Ein Karem, Jerusalem 91120, Israel
  • Michael Schlafman
    • Kfar Shaul Hospital, Jerusalem, Israel
  • Abe Dorevitch
    • Talbieh Hospital, Jerusalem, Israel
  • Avraham Yakir
    • Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah – Hebrew University Medical Center, Ein Karem, Jerusalem 91120, Israel
  • Arturo Lerner
    • Lev Hasharon Hospital, Pardessia, Israel
  • Tanya Goltser
    • Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah – Hebrew University Medical Center, Ein Karem, Jerusalem 91120, Israel
  • Aida Shelevoy
    • Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah – Hebrew University Medical Center, Ein Karem, Jerusalem 91120, Israel
  • Bernard Lerer
    • Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah – Hebrew University Medical Center, Ein Karem, Jerusalem 91120, Israel
Original Investigation

DOI: 10.1007/s002130000521

Cite this article as:
Segman, R., Heresco-Levy, U., Finkel, B. et al. Psychopharmacology (2000) 152: 408. doi:10.1007/s002130000521

Abstract.

Rationale: Tardive dyskinesia (TD) is a long-term adverse effect of dopamine receptor blockers. The dopamine D3 receptor gene (DRD3) ser9gly polymorphism has been previously associated with susceptibility to TD. Serotonin receptor antagonism has been proposed as a common mechanism contributing to the low extrapyramidal effects profile of atypical antipsychotic drugs. Objectives: To examine the association of a functional polymorphism in the 5-HT2C receptor gene (HT2CR) with TD and the joint contribution of HT2CR and DRD3 to susceptibility. Methods: Case control association analysis of allele and genotype frequencies among schizophrenia patients with (n=55) and without TD (n=60), matched for antipsychotic drug exposure and other relevant variables, and normal control subjects (n=97). Parametric analyses of the contribution of 5-HT2Cser and DRD3gly alleles to dyskinesia scores. Results: We found a significant excess of 5-HT2Cser alleles in schizophrenia patients with TD (27.2%) compared to patients without TD (14.6%) and normal controls (14.2%; χ2=6.4, df 2, P=0.03) which was due to the female patients (χ2=8.6, df 2, P=0.01). Among the female TD patients there was an excess of cys-ser and ser-ser genotypes (χ2=11.9, df 4, P=0.02). Analysis of covariance (ANCOVA), controlling for age at first antipsychotic treatment, revealed a significant effect of 5-HT2C genotype on orofacial dyskinesia (OFD) scores (F=3.47, df 2, P=.03). In a stepwise multiple regression analysis, 5-HT2C and DRD3 genotype (5-HT2Cser and DRD3gly allele carriage) respectively contributed 4.2% and 4.7% to the variance in OFD scores. Conclusions: These findings support a small but significant contribution of the HT2CR and DRD3 to susceptibility to TD, which is additive in nature.

Tardive dyskinesia Schizophrenia Serotonin 5-HT2C receptor gene (HT2CR) Dopamine D3 receptor gene (DRD3) Genetic association Complex phenotype Pharmacogenetic

Copyright information

© Springer-Verlag 2000