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Several genome-wide linkage studies have suggested linkage between markers on the long arm of chromosome 22 and schizophrenia. It has also been reported that 22q11.2 deletions increase the risk of schizophrenia. Therefore, 22q is a candidate region for schizophrenia. To search for genetic susceptibility loci for schizophrenia on 22q, we conducted a three-stage case-control association study in Japanese individuals. In the first stage, we examined 13 microsatellite markers on 22q in 766 individuals (340 patients with schizophrenia and 426 control individuals) and found a potential association of AFM262VH5 (D22S283) with schizophrenia. In the second stage, we performed fine mapping of the myosin heavy chain 9, non-muscle (MYH9) gene, where AFM262VH5 is located, using 25 tagging single nucleotide polymorphisms (SNPs). We obtained potential associations between three SNPs in MYH9 and schizophrenia in 1193 individuals (595 patients and 598 controls), which included the individuals analyzed in the first stage. In the third stage, however, we could not replicate these associations in 4694 independent individuals (2288 patients and 2406 controls). Our results suggest that MYH9 does not confer increased susceptibility to schizophrenia in the Japanese population, although we could not exclude possible contributions of other genes on 22q to the pathogenesis of schizophrenia. [ABSTRACT FROM AUTHOR]

The dopamine D3 receptor (DRD3) has been suggested to be involved in the pathophysiology of schizophrenia. DRD3 has been tested for an association with schizophrenia, but with conflicting results. A recent meta-analysis suggested that the haplotype T-T-T-G for the SNPs rs7631540-rs1486012-rs2134655-rs963468 may confer protection against schizophrenia. However, almost all previous studies of the association between DRD3 and schizophrenia have been performed using a relatively small sample size and a limited number of markers. To assess whether DRD3 is implicated in vulnerability to schizophrenia, we conducted case-control association studies and performed an updated meta-analysis. In the first population (595 patients and 598 controls), we examined 16 genotyped single nucleotide polymorphisms (SNPs), including tagging SNPs selected from the HapMap database and SNPs detected through resequencing, as well as 58 imputed SNPs that are not directly genotyped. To confirm the results obtained, we genotyped the SNPs rs7631540-rs1486012-rs2134655-rs963468 in a second, independent population (2126 patients and 2228 controls). We also performed an updated meta-analysis of the haplotype, combining the results obtained in five populations, with a total sample size of 7551. No supportive evidence was obtained for an association between DRD3 and schizophrenia in our Japanese subjects. Our updated meta-analysis also failed to confirm the existence of a protective haplotype. To draw a definitive conclusion, further studies using larger samples and sufficient markers should be carried out in various ethnic populations. [ABSTRACT FROM AUTHOR]

Aims: Although the relationship between body mass index and all-cause mortality is U-shaped, underweight has received comparatively less attention than obesity. There is only limited evidence to date regarding underweight among patients with schizophrenia. This is the first meta-analysis to address the prevalence of underweight in these patients., Methods: We conducted database searches (PubMed, PsycINFO) to identify studies examining underweight in patients with schizophrenia. In total, 17 studies (18 groups) with 45,474 patients were included; data were extracted independently by two authors. A meta-analysis was performed to calculate the pooled prevalence of underweight in patients., Results: The pooled prevalence of underweight was 6.2% (95% CI=4.5-8.6) for the 18 groups, which included 45,474 patients with schizophrenia. The heterogeneity was I 2 =98.9% (95% Cl=98.7-99.1%). Four studies with 4 groups, consisting of 30,014 individuals, focused on Japanese inpatients with schizophrenia. The pooled prevalence of underweight among inpatients in these 4 groups was 17.6% (95% CI=15.5-20.0). Fourteen studies were conducted with non-Japanese inpatients and included 14 groups of 15,460 patients with schizophrenia. The pooled prevalence of underweight in non-Japanese inpatients was 4.6% (95% CI=3.9-5.4). The proportion of underweight in the 18 groups significantly varied between Japanese inpatients and other patients., Conclusions: The results indicated that Japanese inpatients with schizophrenia have a high proportion of underweight. Future research should focus on evaluating interventions that target underweight., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Patients with schizophrenia have a higher risk of metabolic syndrome (MetS). MetS prevalence varies with ethnicity. Although environmental factors, such as lack of physical activity and unbalanced diet, can lead to MetS, these may differ between outpatients and inpatients with schizophrenia. The Japanese mental health care system differs from that in other countries. However, few studies have investigated the prevalence of MetS in Japanese patients with schizophrenia. Therefore, we conducted a nationwide survey to clarify the prevalence of MetS in Japanese outpatients and inpatients with schizophrenia. We investigated the risk of MetS by questionnaire in 520 facilities for outpatients and 247 facilities for inpatients. There were 7655 outpatients and 15,461 inpatients with schizophrenia. MetS prevalence was based on the National Cholesterol Education Program Adult Treatment Panel III (ATP III-A) and the Japan Society for the Study of Obesity (JASSO). The overall MetS prevalence in outpatients using the ATP III-A definition was 34.2%, with 37.8% in men and 29.4% in women, compared with 13.0% in inpatients, with 12.3% in men and 13.9% in women. MetS prevalence in outpatients was approximately 2- to 3-fold higher than in inpatients. In conclusion, MetS prevalence in Japanese outpatients was approximately 3-fold higher than in inpatients. Therefore, we should pay more attention to the risk of physical disease in Japanese patients with schizophrenia, considering the difference in health characteristics between outpatients and inpatients., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Although second-generation antipsychotics (SGAs) are characterized by fewer prolactin (PRL)-related side effects compared with first-generation antipsychotics, the detailed effects of SGAs on the plasma PRL levels still remain unclear. We examined the differences in plasma PRL levels among 268 patients treated for schizophrenia with olanzapine (OLZ), risperidone (RIS), aripiprazole (ARP), quetiapine (QTP), or perospirone (PER). The participants had received antipsychotic monotherapy with stable doses of OLZ, RIS, ARP, QTP, or PER for ≥ 3 weeks, and fasting blood samples were drawn to examine plasma PRL levels. The differences in median plasma PRL levels in all (P<0.001), male (P<0.001) and female patients (P<0.001) among the five SGA groups were statistically significant. A stepwise multiple regression analysis showed that ARP treatment was found to contribute to lower plasma PRL level, while female sex, RIS, OLZ and chlorpromazine equivalent dose were found to contribute to a higher plasma PRL level. The median value of plasma PRL level in the RIS group was twice as much compared with that in the OLZ group, although this was not statistically significant. In this study, OLZ had a considerable effect on plasma PRL level, similar to RIS, while PER did not affect plasma PRL levels, similar to QTP. Further studies are needed to clarify the differences in plasma PRL levels among SGAs., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Gene expression profiling with microarray technology suggests that peripheral blood cells might be a surrogate for postmortem brain tissue in studies of schizophrenia. The development of an accessible peripheral biomarker would substantially help in the diagnosis of this disease. We used a bioinformatics approach to examine whether the gene expression signature in whole blood contains enough information to make a specific diagnosis of schizophrenia. Unpaired t-tests of gene expression datasets from 52 antipsychotics-free schizophrenia patients and 49 normal controls identified 792 differentially expressed probes. Functional profiling with DAVID revealed that eleven of these genes were previously reported to be associated with schizophrenia, and 73 of them were expressed in the brain tissue. We analyzed the datasets with one of the supervised classifiers, artificial neural networks (ANNs). The samples were subdivided into training and testing sets. Quality filtering and stepwise forward selection identified 14 probes as predictors of the diagnosis. ANNs were then trained with the selected probes as the input and the training set for known diagnosis as the output. The constructed model achieved 91.2% diagnostic accuracy in the training set and 87.9% accuracy in the hold-out testing set. On the other hand, hierarchical clustering, a standard but unsupervised classifier, failed to separate patients and controls. These results suggest analysis of a blood-based gene expression signature with the supervised classifier, ANNs, might be a diagnostic tool for schizophrenia., (Copyright (c) 2009 Elsevier B.V. All rights reserved.)

Systematic linkage disequilibrium (LD) mapping of 8p12-21 in the Icelandic population identified neuregulin 1 (NRG1) as a prime candidate gene for schizophrenia. However, results of replication studies have been inconsistent, and no large sample analyses have been reported. Therefore, we designed this study with the aim of assessing this putative association between schizophrenia and NRG1 (especially HAP(ICE) region and exon region) using a gene-based association approach in the Japanese population. This study was a two-stage association analysis with a different panel of samples, in which the significant association found in the first-set screening samples (1126 cases and 1022 controls) was further assessed in the confirmation samples (1262 cases and 1172 controls, and 166 trio samples). In the first-set scan, 60 SNPs (49 tagging SNPs from HapMap database, four SNPs from other papers, and seven SNPs detected in the mutation scan) were examined. One haplotype showed a significant association in the first-set screening samples (Global P-value=0.0244, uncorrected). However, we could not replicate this association in the following independent confirmation samples. Moreover, we could not find sufficient evidence for association of the haplotype identified as being significant in the first-set samples by imputing ungenotyped SNPs from HapMap database. These results indicate that the positionally and functionally attractive regions of NRG1 are unlikely to contribute to susceptibility to schizophrenia in the Japanese population. Moreover, the nature of our results support that two-stage analysis with large sample size is appropriate to examine the susceptibility genes for common diseases.

Introduction: Glutamate dysfunction has been implicated in the pathophysiology of schizophrenia. The metabotropic glutamate receptors (mGluRs) are G-protein-coupled receptors. GRM7, the gene that encodes mGluR7, is expressed in many regions of the human central nervous system. The GRM7 gene is located on human chromosome 3p26, which has been suggested by linkage analysis to contain a susceptibility locus for schizophrenia., Methods: We screened for mutations in all exons, exon/intron junctions, and promoter regions of the GRM7 gene in Japanese patients with schizophrenia and evaluated associations between the detected polymorphisms and schizophrenia. We examined the influence of one polymorphism associated with schizophrenia on the expression of GRM7 by dual-luciferase assay in transfected cells., Results: Twenty-five polymorphisms/mutations were detected in GRM7. Case-control analysis revealed a potential association of a synonymous polymorphism (371T/C, rs3749380) in exon 1 with schizophrenia in our case-control study of 2293 Japanese patients with schizophrenia and 2382 Japanese control subjects (allelic p=0.009). Dual-luciferase assay revealed suppression of transcription activity by exon 1 containing this polymorphism and a statistically significant difference in the promoter activity between the T and C alleles., Conclusions: Our results support the possible association of a GRM7 gene polymorphism with genetic susceptibility to schizophrenia.

Brain-derived neurotrophic factor (BDNF) plays important roles in the survival, maintenance and growth of neurons. Several studies have indicated that BDNF is likely to be related to the pathogenesis of schizophrenia. Recent genetic analyses have revealed that BDNF gene polymorphisms are associated with schizophrenia, although contradictory negative findings have also been reported. To assess whether three BDNF gene polymorphisms (rs988748, C132T and rs6265) could be implicated in vulnerability to schizophrenia, we conducted a case-control association analysis (349 patients and 423 controls) in Japanese subjects. We found no association between these BDNF gene polymorphisms and schizophrenia using both single-marker and haplotype analyses. The results of the present study suggest that these three BDNF gene polymorphisms do not play major roles in conferring susceptibility to schizophrenia in a Japanese population. However, further studies assessing the associations between these BDNF gene polymorphisms and schizophrenia should be performed in several other ethnic populations.