title: Analysis of genetic variations in the dopamine D1 receptor (DRD1) gene and antipsychotics-induced tardive dyskinesia in schizophrenia.
abstract: BACKGROUND
  Dyskinesia is a kind of abnormal involuntary movement disorder that increases with age. The pathogenesis of dyskinesia may result from divergent changes in dopamine D1 receptors (DRD1) and dopamine D2 receptors (DRD2) in the brain while aging. Tardive dyskinesia (TD), a kind of dyskinesia, may develop after long-term antipsychotic treatment. Because the prevalence of TD also steadily increased with age, TD has been suggested to be the consequence of an imbalance between DRD1 and DRD2. We supposed that patients who develop TD may have genetic variants of DRD1 that cause the excitatory effects of DRD1 overwhelming the attenuated inhibitory effects of DRD2 after antipsychotic treatment.
  
  
  METHODS
  In the present study, schizophrenic inpatients receiving long-term antipsychotic treatment were first assessed using the Abnormal Involuntary Movement Scale (AIMS), and only patients who were either free of any abnormal involuntary movements (non-TD group, AIMS =0) or who showed persistent TD (TD group) were enrolled. Finally, 382 patients were recruited (TD=220, non-TD=162) and three single nucleus polymorphisms (SNPs; rs5326, rs4532 and rs265975) of DRD1 were genotyped for each subject.
  
  
  RESULTS
  Genotype frequency (%; AA/AG/GG) of rs4532 (TD: non-TD) was 61.4/35.8/2.8: 74.2/24.5/1.3. After genetic analyses, genotype GG showed significant association with TD (if OR=2.0, power (%)=98.5; if OR=1.5, power (%)=63.7; P=0.033). Haplotype frequency (%) CGC of rs5326-rs4532-rs265975 (TD: non-TD) was 19.0:13.7; and after haplotype-based analyses, haplotype CGC also showed significant association with TD (OR=1.4, permutation P=0.027).
  
  
  CONCLUSIONS
  Our results indicate that the genotypic variants of DRD1 might play a role in the susceptibility of TD. Further replication in other countries or other populations is highly expected.
authors.affiliation: Department of Psychiatry, Tzu Chi General Hospital, Hualien, Taiwan.|Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.
authors.forename: I-Ching
authors.initials: IC
authors.lastname: Lai
authors.affiliation: Department of Psychiatry, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Geng-Han
authors.initials: GH
authors.lastname: Mo
authors.affiliation: Department of Research, Tzu Chi General Hospital, Taipei, Taiwan.
authors.forename: Mao-Liang
authors.initials: ML
authors.lastname: Chen
authors.affiliation: Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.|Department of Psychiatry, Yuli Veterans Hospital, Hualien, Taiwan.
authors.forename: Ying-Chieh
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, Yuli Veterans Hospital, Hualien, Taiwan.
authors.forename: Jen-Yeu
authors.initials: JY
authors.lastname: Chen
authors.affiliation: Department of Psychiatry, Pali Psychiatric Hospital, Taipei, Taiwan.
authors.forename: Ding-Lieh
authors.initials: DL
authors.lastname: Liao
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Sec. 2, 11217, Taipei, Taiwan.
authors.forename: Ya-Mei
authors.initials: YM
authors.lastname: Bai
authors.affiliation: Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chao-Cheng
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Department of Psychiatry, Yuli Veterans Hospital, Hualien, Taiwan.
authors.forename: Tzu-Ting
authors.initials: TT
authors.lastname: Chen
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Sec. 2, 11217, Taipei, Taiwan. yjliou@mail2000.com.tw.|Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan. yjliou@mail2000.com.tw.
authors.forename: Ying-Jay
authors.initials: YJ
authors.lastname: Liou
mesh_terms: D014150:Antipsychotic Agents / Q000009:adverse effects*; D004409:Dyskinesia, Drug-Induced / Q000150:complications / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D017447:Receptors, Dopamine D1 / Q000235:genetics*; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy* / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: D014150:Antipsychotic Agents; D017447:Receptors, Dopamine D1