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

  • Ronnen H. Segman
  • Uriel Heresco-Levy
  • Boris Finkel
  • Roi Inbar
  • Tal Neeman
  • Michael Schlafman
  • Abe Dorevitch
  • Avraham Yakir
  • Arturo Lerner
  • Tanya Goltser
  • Aida Shelevoy
  • Bernard Lerer
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

Authors and Affiliations

  • Ronnen H. Segman
    • 1
  • Uriel Heresco-Levy
    • 2
  • Boris Finkel
    • 3
  • Roi Inbar
    • 1
  • Tal Neeman
    • 1
  • Michael Schlafman
    • 4
  • Abe Dorevitch
    • 5
  • Avraham Yakir
    • 1
  • Arturo Lerner
    • 3
  • Tanya Goltser
    • 1
  • Aida Shelevoy
    • 1
  • Bernard Lerer
    • 1
  1. 1.Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah – Hebrew University Medical Center, Ein Karem, Jerusalem 91120, Israel
  2. 2.Herzog Hospital, Jerusalem, Israel
  3. 3.Lev Hasharon Hospital, Pardessia, Israel
  4. 4.Kfar Shaul Hospital, Jerusalem, Israel
  5. 5.Talbieh Hospital, Jerusalem, Israel