Genetic association between G protein-coupled receptor kinase 6/β-arrestin 2 and dopamine supersensitivity psychosis in schizophrenia
Yasunori Oda,1 Nobuhisa Kanahara,2 Hiroshi Kimura,1 Hiroyuki Watanabe,2 Kenji Hashimoto,3 Masaomi Iyo1 1Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan; 2Division of Medical Treatment and Rehabilitation, 3Division of Clinical Neuroscience, Chiba University Cente...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2015-07-01
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| Series: | Neuropsychiatric Disease and Treatment |
| Online Access: | http://www.dovepress.com/genetic-association-between-g-protein-coupled-receptor-kinase-6beta-ar-peer-reviewed-article-NDT |
| _version_ | 1819044074853761024 |
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| author | Oda Y Kanahara N Kimura H Watanabe H Hashimoto K Iyo M |
| author_facet | Oda Y Kanahara N Kimura H Watanabe H Hashimoto K Iyo M |
| author_sort | Oda Y |
| collection | DOAJ |
| description | Yasunori Oda,1 Nobuhisa Kanahara,2 Hiroshi Kimura,1 Hiroyuki Watanabe,2 Kenji Hashimoto,3 Masaomi Iyo1 1Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan; 2Division of Medical Treatment and Rehabilitation, 3Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan Background/aim: 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. Conclusion: 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. Keywords: antipsychotic, dopamine D2 receptor, tardive dyskinesia, treatment-resistant |
| first_indexed | 2024-12-21T10:06:54Z |
| format | Article |
| id | doaj.art-3c0baeec298e466c893d54ad07d6d8b9 |
| institution | Directory Open Access Journal |
| issn | 1178-2021 |
| language | English |
| last_indexed | 2024-12-21T10:06:54Z |
| publishDate | 2015-07-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Neuropsychiatric Disease and Treatment |
| spelling | doaj.art-3c0baeec298e466c893d54ad07d6d8b92022-12-21T19:07:49ZengDove Medical PressNeuropsychiatric Disease and Treatment1178-20212015-07-012015default1845185122848Genetic association between G protein-coupled receptor kinase 6/β-arrestin 2 and dopamine supersensitivity psychosis in schizophreniaOda YKanahara NKimura HWatanabe HHashimoto KIyo MYasunori Oda,1 Nobuhisa Kanahara,2 Hiroshi Kimura,1 Hiroyuki Watanabe,2 Kenji Hashimoto,3 Masaomi Iyo1 1Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan; 2Division of Medical Treatment and Rehabilitation, 3Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan Background/aim: 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. Conclusion: 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. Keywords: antipsychotic, dopamine D2 receptor, tardive dyskinesia, treatment-resistanthttp://www.dovepress.com/genetic-association-between-g-protein-coupled-receptor-kinase-6beta-ar-peer-reviewed-article-NDT |
| spellingShingle | Oda Y Kanahara N Kimura H Watanabe H Hashimoto K Iyo M Genetic association between G protein-coupled receptor kinase 6/β-arrestin 2 and dopamine supersensitivity psychosis in schizophrenia Neuropsychiatric Disease and Treatment |
| title | Genetic association between G protein-coupled receptor kinase 6/β-arrestin 2 and dopamine supersensitivity psychosis in schizophrenia |
| title_full | Genetic association between G protein-coupled receptor kinase 6/β-arrestin 2 and dopamine supersensitivity psychosis in schizophrenia |
| title_fullStr | Genetic association between G protein-coupled receptor kinase 6/β-arrestin 2 and dopamine supersensitivity psychosis in schizophrenia |
| title_full_unstemmed | Genetic association between G protein-coupled receptor kinase 6/β-arrestin 2 and dopamine supersensitivity psychosis in schizophrenia |
| title_short | Genetic association between G protein-coupled receptor kinase 6/β-arrestin 2 and dopamine supersensitivity psychosis in schizophrenia |
| title_sort | genetic association between g protein coupled receptor kinase 6 beta arrestin 2 and dopamine supersensitivity psychosis in schizophrenia |
| url | http://www.dovepress.com/genetic-association-between-g-protein-coupled-receptor-kinase-6beta-ar-peer-reviewed-article-NDT |
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