I-Ching Lai1,2, Geng-Han Mo3, Mao-Liang Chen4, Ying-Chieh Wang2,5, Jen-Yeu Chen5, Ding-Lieh Liao6, Ya-Mei Bai7, Chao-Cheng Lin8, Tzu-Ting Chen5, Ying-Jay Liou9,10. 1. Department of Psychiatry, Tzu Chi General Hospital, Hualien, Taiwan. 2. Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan. 3. Department of Psychiatry, Changhua Christian Hospital, Changhua, Taiwan. 4. Department of Research, Tzu Chi General Hospital, Taipei, Taiwan. 5. Department of Psychiatry, Yuli Veterans Hospital, Hualien, Taiwan. 6. Department of Psychiatry, Pali Psychiatric Hospital, Taipei, Taiwan. 7. Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Sec. 2, 11217, Taipei, Taiwan. 8. Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan. 9. Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Sec. 2, 11217, Taipei, Taiwan. yjliou@mail2000.com.tw. 10. Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan. yjliou@mail2000.com.tw.
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). CONCLUSION: 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.
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). CONCLUSION: 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.
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