title: Association of two DRD2 gene polymorphisms with acute and tardive antipsychotic-induced movement disorders in young Caucasian patients.
abstract: BACKGROUND
  Pharmacogenetic studies on antipsychotic-induced movement disorders (MD) in schizophrenia so far have focused mainly on tardive dyskinesia. Only a few examined the more acute antipsychotic-induced MD such as parkinsonism and akathisia. Notably, all MD relate to deregulation of the dopamine system.
  
  
  OBJECTIVE
  This study aimed to replicate previously reported associations in candidate genes for acute and tardive antipsychotic-induced MD in a young Caucasian sample.
  
  
  METHODS
  In 402 patients (median age 26 years), a total of 13 polymorphisms were genotyped in eight dopamine-related candidate genes selected a priori from the literature (regarding dopamine and serotonin receptors, dopamine degradation, and free radicals scavenging enzymes pathways).
  
  
  RESULTS
  Patients with MD used on average a higher haloperidol dose equivalent when compared to those without MD. The prevalence of MD was high and did not differ between first- and second-generation antipsychotics. Significant associations were found between (a) the TaqI_D polymorphism and akathisia (OR = 2.3, p = 0.001 for each extra C-allele) and (b) the -141C polymorphism and tardive dyskinesia (OR = 0.20, p = 0.001 for each extra Del allele). The other polymorphisms were not significantly associated with an MD.
  
  
  CONCLUSIONS
  Two associations were found between genetic variation TaqI_D and the -141C polymorphisms in the DRD2 gene and antipsychotic-induced MD; one with acute akathisia and one with tardive dyskinesia. These were previously reported to be associated with tardive dyskinesia and acute parkinsonism, respectively. These results suggest that the contribution of these DRD2 gene variants in the vulnerability of antipsychotic-induced MD takes place in a more general or pleiotropic way.
authors.affiliation: Mental Health Organization GGZ Centraal, Amersfoort, the Netherlands.
authors.forename: Jeroen P
authors.initials: JP
authors.lastname: Koning
authors.forename: Jelle
authors.initials: J
authors.lastname: Vehof
authors.forename: Huibert
authors.initials: H
authors.lastname: Burger
authors.forename: Bob
authors.initials: B
authors.lastname: Wilffert
authors.forename: Asmar
authors.initials: A
authors.lastname: Al Hadithy
authors.forename: Behrooz
authors.initials: B
authors.lastname: Alizadeh
authors.forename: Peter N
authors.initials: PN
authors.lastname: van Harten
authors.forename: Harold
authors.initials: H
authors.lastname: Snieder
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects*; D004409:Dyskinesia, Drug-Induced / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009069:Movement Disorders / Q000175:diagnosis / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2