Combined analysis of 635 patients confirms an age-related association of the serotonin 2A receptor gene with tardive dyskinesia and specificity for the non-orofacial subtype

Bernard Lerer*, Ronnen H. Segman, Ene Choo Tan, Vincenzo S. Basile, Roberto Cavallaro, Harald N. Aschauer, Rael Strous, Siow Ann Chong, Uriel Heresco-Levy, Massimiliano Verga, Joachim Scharfetter, Herbert Y. Meltzer, James L. Kennedy, Fabio Macciardi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

Tardive dyskinesia (TD) is an important limiting factor in the use of typical antipsychotic drugs. Genetic variability in the serotonin 2A (5-HT 2A) receptor may influence risk for TD but the results of prior studies are not confirmatory. The objective of this study was to determine association of T102C and His452Tyr polymorphisms in the 5-HT 2A receptor gene (HTR 2A) with TD in a large, multicentre patient sample. The design employed case-control analysis controlling for possible confounders using pooled, original data from published and available unpublished samples and employing logistic regression, analysis of variance and meta-analysis. The study sample consisted of 635 patients with schizophrenia or schizoaffective disorder (256 with TD and 379 without TD) drawn from five research centres, divided into six groups based on population origin. The main outcome measure was association of a categorical diagnosis of TD based on the Research Diagnostic Criteria for TD with HTR 2A T102C and His452Tyr genotypes and haplotypes. The findings indicate significant association of TD with HTR 2A T102C genotype (p = 0.002) over and above the effect of population group, also when controlling for age and gender (p = 0.0008), but not with His452Tyr genotype. The T102C genotype was significantly associated with TD in older (> median age 47 yr, p = 0.002) but not younger patients and in patients with non-orofacial (limb-truncal) (p = 0.001) but not orofacial TD. By meta-analysis the Mantel-Haenszel (M-H) pooled odds ratio (OR) across all the available data was 1.64. A T102C-His452Tyr haplotype was significantly associated with TD (p = 0.0008). These findings confirm that genetic variability in HTR 2A contributes a small but significant degree of risk for the expression of TD, particularly in older patients and specifically for the non-orofacial (limb-truncal) type. Together with other genetic variants associated with TD the findings could be used to assess risk in patients who are candidates for treatment with typical antipsychotic medications.

Original languageEnglish (US)
Pages (from-to)411-425
Number of pages15
JournalInternational Journal of Neuropsychopharmacology
Volume8
Issue number3
DOIs
StatePublished - Sep 2005

Keywords

  • Antipsychotic drugs
  • Molecular genetics
  • Pharmacogenetics
  • Pharmacogenomics
  • Schizophrenia
  • Serotonin 2a (5-HT ) receptors
  • Single nucleotide polymorphism
  • Tardive dyskinesia

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Combined analysis of 635 patients confirms an age-related association of the serotonin 2A receptor gene with tardive dyskinesia and specificity for the non-orofacial subtype'. Together they form a unique fingerprint.

Cite this