Association of dopamine D3-receptor gene variants with neuroleptic induced akathisia in schizophrenic patients: a generalization of Steen's study on DRD3 and tardive dyskinesia

Am J Med Genet. 2000 Apr 3;96(2):187-91. doi: 10.1002/(sici)1096-8628(20000403)96:2<187::aid-ajmg13>3.0.co;2-8.

Abstract

Neuroleptic induced akathisia is a common and distressful extrapyramidal side effect of antipsychotic treatment. A significant proportion of the variability of its development has been left unexplained and has to be attributed to individual susceptibility. Since hereditary factors have been discussed in the etiology of acute akathisia (AA), part of the individual susceptibility might be of genetic origin. Moreover, AA is regarded as a forerunner of tardive dyskinesia, a drug-induced chronic movement disorder, which may be associated with homozygosity for the Ser9Gly variant of the DRD3 gene. Considering expression studies, which demonstrated functional variants of DRD3 polymorphisms, we investigated whether homozygosity for the Ser9Gly variant of the DRD3 gene is associated with AA. Homozygosity for the Ser9Gly variant of the DRD3 gene was connected to an 88% incidence of AA as compared with a considerably lower 46.9% incidence of AA in schizophrenic patients nonhomozygous for the 2-2 allele (exact P = 0.0223). Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:187-191, 2000.

Publication types

  • Comparative Study

MeSH terms

  • Acute Disease
  • Akathisia, Drug-Induced / etiology
  • Akathisia, Drug-Induced / genetics*
  • Amino Acid Substitution
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use
  • Dyskinesias / etiology
  • Dyskinesias / genetics*
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • Genetic Variation / genetics*
  • Germany
  • Haloperidol / adverse effects
  • Haloperidol / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic / genetics
  • Receptors, Dopamine D2 / genetics*
  • Receptors, Dopamine D3
  • Schizophrenia / drug therapy
  • Schizophrenia / genetics*

Substances

  • Antipsychotic Agents
  • DRD3 protein, human
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Haloperidol