Mutation screening and association study of the beta-adrenergic receptor kinase 2 gene in schizophrenia families.

Chromosome 22q12 is one of the most promising regions for harboring a risk gene for schizophrenia. We have reported significant linkage of intermediate phenotypes for schizophrenia with markers within or near the beta-adrenergic receptor kinase 2 (ADRBK2, or GRK3) gene, which is highly expressed in dopaminergic pathways in the central nervous system, and mediates homologous desensitization for a variety of neurotransmitters and hormones through phosphorylation of G protein-coupled receptors (GPCRs). A polymorphism in the promoter region of the ADRBK2 was reported to be associated with bipolar disorder. We screened the putative promoter region, and all 21 exonic and flanking intronic regions of the ADRBK2 gene for mutations in 48 schizophrenia probands (including 16 Japanese and 32 Chinese patients), and evaluated the detected polymorphisms and those reported in the JSNP database for associations with schizophrenia in 113 family trios of schizophrenia probands. Four single nucleotide variants in the 5'-UTR/promoter region, and 16 rare variants in exonic and flanking regions, were identified. Among them, the Cys208Ser variant was the only non-synonymous mutation. Cys208Ser was found in one family without cosegregation between the variant and schizophrenia. Moreover, allelic, genotypic and haplotypic analyses provided no evidence for association between alleles at these polymorphisms and schizophrenia. The present study indicates that the ADRBK2 gene is unlikely to contribute strongly to schizophrenia susceptibility in this set of families.

Determining vulnerability to schizophrenia in methamphetamine psychosis using exploratory eye movements.

Patients with methamphetamine (MAP) psychosis whose psychotic symptoms continued after MAP withdrawal were observed at Saitama Prefecture Government Psychiatric Hospital. The purpose of the present study was to ascertain whether some of these MAP psychosis subjects have a vulnerability to schizophrenia. Forty-eight patients with MAP psychosis were divided into three groups based on clinical course: transient type, prolonged type and persistent type. Furthermore, the patients with the persistent type were divided into two groups: one group were moderately disturbed in social adaptive functioning and had Global Assessment Functioning scale (GAF) points >50, and the other group consisted of those who were severely disturbed in social adaptive functioning and who had GAF points of < or =50. These MAP patients were tested for exploratory eye movements, which are the vulnerability marker of schizophrenia, and were compared with 30 patients with schizophrenia and 30 healthy control subjects. The responsive search score of the severely disturbed group of patients of the persistent type was lowest, significantly lower than those of the transient type and the healthy controls. It did not differ from that of the schizophrenic subjects. These results suggest that the severely disturbed group of patients with the persistent type of MAP psychosis have a vulnerability to schizophrenia.