| 1 | Synapse 2006 Aug 60: 141-51 |
|---|---|
| PMID | 16715494 |
| Title | Antipsychotic pathway genes with expression altered in opposite direction by antipsychotics and amphetamine. |
| Abstract | To develop a new strategy for identifying possible psychotic- or antipsychotic-related pathway genes, rats were treated with clinical doses of haloperidol and clozapine for 4 days, and the altered expression of genes was compared with the genes altered in expression after amphetamine sensitization. The objective was to identify genes with expression altered in the same direction by haloperidol and clozapine but in the opposite direction in the amphetamine-sensitized rat striatum. These criteria were met by 21 genes, consisting of 15 genes upregulated by amphetamine, and 6 genes downregulated by amphetamine. Of the 21 genes, 15 are not presently identified, and only 3 genes (cathepsin K, GRK6, and a gene with accession number AI177589) are located in chromosome regions known to be associated with schizophrenia. |
| SCZ Keywords | schizophrenia |
| 2 | Neurobiol. Dis. 2011 Nov 44: 248-58 |
| PMID | 21784156 |
| Title | Reduced expression of G protein-coupled receptor kinases in schizophrenia but not in schizoaffective disorder. |
| Abstract | Alterations of multiple G protein-mediated signaling pathways are detected in schizophrenia. G protein-coupled receptor kinases (GRKs) and arrestins terminate signaling by G protein-coupled receptors exerting a powerful influence on receptor functions. Modifications of arrestin and/or GRKs expression may contribute to schizophrenia pathology. Cortical expression of arrestins and GRKs was measured postmortem in control and subjects with schizophrenia or schizoaffective disorder. Additionally, arrestin/GRK expression was determined in elderly patients with schizophrenia and age-matched control. Patients with schizophrenia, but not schizoaffective disorder, displayed a reduced concentration of arrestin and GRK mRNAs and GRK3 protein. Arrestins and GRK significantly decreased with age. In elderly patients, GRK6 was reduced, with other GRKs and arrestins unchanged. A reduced cortical concentration of GRKs in schizophrenia (resembling that in aging) may result in altered G protein-dependent signaling, thus contributing to prefrontal deficits in schizophrenia. The data suggest distinct molecular mechanisms underlying schizophrenia and schizoaffective disorder. |
| SCZ Keywords | schizophrenia |
| 3 | Hum Psychopharmacol 2014 Jan 29: 100-3 |
| PMID | 24302161 |
| Title | Association study of common variants within the G protein-coupled receptor kinase 6 gene and schizophrenia susceptibility in Han Chinese. |
| Abstract | In this study, we examined whether common variants in the G protein-coupled receptor kinase 6 gene (GRK6) confers susceptibility to schizophrenia in Chinese. We genotyped two common variants in 697 schizophrenia patients and 563 healthy control subjects. No significant difference in either allele or genotype comparisons between the case and control groups was found. Our results imply that GRK6 may not play a role in the pathophysiology of schizophrenia among Han Chinese. |
| SCZ Keywords | schizophrenia |
| 4 | Neuropsychiatr Dis Treat 2015 -1 11: 1845-51 |
| PMID | 26251601 |
| Title | Genetic association between G protein-coupled receptor kinase 6/?-arrestin 2 and dopamine supersensitivity psychosis in schizophrenia. |
| Abstract | 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 ?-arrestin 2 (ARRB2) that are involved in the trafficking of DRD2 in patients with DSP. 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). 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. 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. |
| SCZ Keywords | schizophrenia |