title: Genetic association between G protein-coupled receptor kinase 6/β-arrestin 2 and dopamine supersensitivity psychosis in schizophrenia.
abstract: OBJECTIVE
  Dopamine supersensitivity psychosis (DSP), clinically characterized by unstable and severe psychosis or tardive dyskinesia and often categorized as treatment-resistant schizophrenia, is promoted by long-term antipsychotic treatment. An upregulation of the dopamine D2 receptor caused by antipsychotic(s) is involved in the development of DSP. The present study explored the potential roles of G protein-coupled receptor kinase 6 (GRK6) and β-arrestin 2 (ARRB2) that are involved in the trafficking of DRD2 in patients with DSP.
  
  
  METHODS
  We conducted a genetic association study of GRK6/ARRB2 between the patients with DSP episodes [DSP(+) group: N=108] and the patients without DSP(-) episodes [DSP(-) group: N=169] from the total group of patients (N=333). Based on the patients' treatment history, a DSP episode was defined as withdrawal psychosis, developed tolerance to antipsychotic effect, and tardive dyskinesia (the remaining 56 patients were excluded due to insufficient information).
  
  
  RESULTS
  The results revealed that none of the allelic or genotyping distributions of five single nucleotide polymorphisms (SNPs) of GRK6 and three SNPs of ARRB2 showed any significant difference between the DSP(+) and DSP(-) groups.
  
  
  CONCLUSIONS
  The results suggest that the SNP analyses of these two molecules fail to classify patients into the potential clinical subtype of DSP(+) or DSP(-) group. However, since GRK6 and ARRB2 are surely involved in dopamine D2 receptor metabolism, further studies based on prospective observations of the onset of DSP under specific antipsychotic treatments are needed.
authors.affiliation: Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Oda
authors.affiliation: Division of Medical Treatment and Rehabilitation, Chiba University Center for Forensic Mental Health, Chiba, Japan.
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Kanahara
authors.affiliation: Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kimura
authors.affiliation: Division of Medical Treatment and Rehabilitation, Chiba University Center for Forensic Mental Health, Chiba, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Hashimoto
authors.affiliation: Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Masaomi
authors.initials: M
authors.lastname: Iyo
keywords: antipsychotic; dopamine D2 receptor; tardive dyskinesia; treatment-resistant