title: Antipsychotic-induced movement disorders in long-stay psychiatric patients and 45 tag SNPs in 7 candidate genes: a prospective study.
abstract: OBJECTIVE
  Four types of antipsychotic-induced movement disorders: tardive dyskinesia (TD), parkinsonism, akathisia and tardive dystonia, subtypes of TD (orofacial and limb truncal dyskinesia), subtypes of parkinsonism (rest tremor, rigidity, and bradykinesia), as well as a principal-factor of the movement disorders and their subtypes, were examined for association with variation in 7 candidate genes (GRIN2B, GRIN2A, HSPG2, DRD3, DRD4, HTR2C, and NQO1).
  
  
  METHODS
  Naturalistic study of 168 white long-stay patients with chronic mental illness requiring long-term antipsychotic treatment, examined by the same rater at least two times over a 4-year period, with a mean follow-up time of 1.1 years, with validated scales for TD, parkinsonism, akathisia, and tardive dystonia. The authors genotyped 45 tag SNPs in 7 candidate genes, associated with movement disorders or schizophrenia in previous studies. Genotype and allele frequency comparisons were performed with multiple regression methods for continuous movement disorders.
  
  
  RESULTS
  Various tag SNPs reached nominal significance; TD with rs1345423, rs7192557, rs1650420, as well as rs11644461; orofacial dyskinesia with rs7192557, rs1650420, as well as rs4911871; limb truncal dyskinesia with rs1345423, rs7192557, rs1650420, as well as rs11866328; bradykinesia with rs2192970; akathisia with rs324035; and the principal-factor with rs10772715. After controlling for multiple testing, no significant results remained.
  
  
  CONCLUSIONS
  The findings suggest that selected tag SNPs are not associated with a susceptibility to movement disorders. However, as the sample size was small and previous studies show inconsistent results, definite conclusions cannot be made. Replication is needed in larger study samples, preferably in longitudinal studies which take the fluctuating course of movement disorders and gene-environment interactions into account.
authors.affiliation: Psychiatric Centre GGZ Centraal, Amersfoort, The Netherlands. robertobakker@gmail.com
authors.forename: P Roberto
authors.initials: PR
authors.lastname: Bakker
authors.forename: Asmar F Y
authors.initials: AF
authors.lastname: Al Hadithy
authors.forename: Najaf
authors.initials: N
authors.lastname: Amin
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: Jim
authors.initials: J
authors.lastname: van Os
authors.forename: Peter N
authors.initials: PN
authors.lastname: van Harten
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D004409:Dyskinesia, Drug-Induced / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012044:Regression Analysis; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents