A susceptibility gene for schizophrenia, dysbindin, is a component of BLOC-1, which interacts with the adaptor protein (AP)-3 complex. As a direct interaction between dysbindin and AP-3 complex was reported, we examined a possible association between 16 SNPs in the AP3 complex genes and schizophrenia using 432 cases and 656 controls. Nominal association between rs6688 in the AP3M1 gene and schizophrenia (chi(2)=6.33, P=0.012, odds ratio=0.80) was no longer positive after correction for multiple testing (corrected P=0.192). The present results suggest that AP3 complex genes might not play a major role in the pathogenesis of schizophrenia in this population.

Increased levels of proinflammatory cytokines have been implicated in schizophrenia; however, their pathophysiological roles in abnormal brain dysfunctions remain unclear. We evaluated the effect of proinflammatory cytokines on a high-fat diet (HFD)-induced prepulse inhibition (PPI) deficits in the acoustic startle response. Eight-week-old male C57BL/6J mice were fed a HFD for 3 weeks and then PPI was examined. HFD significantly induced PPI deficits and increased plasma IL-6, but not TNFα, levels. Interestingly, MR16-1 administration during the HFD period ameliorated PPI deficits. Further, in the striatum of HFD-fed mice, phosphorylation of GSK3β, but not GSK3α, was significantly increased; this increase was attenuated by MR16-1, although the protein levels of GSK3α and β were not altered. There were no significant differences in either phosphorylation or protein levels of GSK3α, β in the PFC during the HFD period. These results suggest that increased IL-6 levels during HFD may induce sensorimotor gating deficits, likely through the alteration of striatal GSK3β phosphorylation. MR16-1 might have a beneficial effect on such HFD-induced sensorimotor gating deficits.

l-Serine is required for the synthesis of glycine and d-serine, both of which are NMDA receptor co-agonists. Although roles for d-serine and glycine have been suggested in schizophrenia, little is known about the role of the l-serine synthesizing cascade in schizophrenia or related psychiatric conditions. Here we report a patient with schizophrenia carrying a balanced chromosomal translocation with the breakpoints localized to 3q13.12 and 9q21.2. We examined this proband and her son with schizotypal personality disorder for chromosomal abnormalities, molecular expression profiles, and serum amino acids. Marked decrease of l-serine and glutamate was observed in the sera of the patient and her son, compared with those in normal controls. Interestingly, expression of PSAT1 gene, which is located next to the breakpoint and encodes one of the enzymes in the l-serine synthesizing cascade, was reduced in both patient and her son. Direct effect of impaired PSAT1 gene expression on decreased serum l-serine level was strongly implicated by rat astrocyte experiments. In summary, we propose an idea that PSAT1 may be implicated in altered serine metabolism and schizophrenia spectrum conditions.

Several evidence suggests that alterations in serotonin 6 (5-HT6) receptors might be associated with the pathophysiology of mood disorders. Therefore, to evaluate the association between HTR6 and BP and MDD, we conducted a case-control study of Japanese population samples (1007 BP patients, 447 MDD patients and 1753 controls) with five tagging SNPs, including rs1805054 (C267T), in HTR6. In addition, we conducted a meta-analysis of rs1805054, which has been examined in other studies. We selected five tagging SNPs (rs6693503, rs1805054, rs4912138, rs3790757 and rs9659997). Moreover, three association studies for BP and four association studies for MDD, including this study, met our criteria for the meta-analysis of rs1805054. We did not detect an association between tagging SNPs in HTR6 and BP and MDD in the allele/genotype, haplotype analysis or meta-analysis. In conclusion, we found no association involving polymorphism and mood disorder in the Japanese population. However, because changes in expression level or signal transduction of this receptor may be involved in the pathology of these diseases, it will be necessary to conduct the further study about the relationship between this receptor and mood disorders in the future.