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Aleksic B.,Nagoya University | Kushima I.,Nagoya University | Ito Y.,Nagoya University | Nakamura Y.,Nagoya University | And 10 more authors.
Schizophrenia Research | Year: 2010

The aim of the current study was to examine the association of KREMEN1 and DKK1, two wnt pathway-related genes with schizophrenia in Japanese subjects. We genotyped 16 common genetic variants within the aforementioned genes and examined their associations with schizophrenia. Results demonstrated that a common variant in the promoter region of KREMEN1 might modulate the risk of schizophrenia in the Japanese. However, further replication will be needed for conclusive interpretation of the effect of this locus on the pathogenesis of schizophrenia. © 2010 Elsevier B.V.

Fukuda S.,Osaka City University | Hashimoto R.,RISTEX JST | Hashimoto R.,The Osaka Hamamatsu Joint Research Center For Child Mental Development | Hashimoto R.,Osaka University | And 18 more authors.
Life Sciences | Year: 2010

Aims: Disrupted-in schizophrenia 1 (DISC1), identified in a pedigree with a familial psychosis with the chromosome translocation (1:11), is a putative susceptibility gene for psychoses such as schizophrenia and major depressive disorder (MDD). Patients with chronic fatigue syndrome (CFS) report having continuous severe fatigue and many overlapping symptoms with MDD; however, the mechanism and effective treatment of CFS are still unclear. We focused on the overlapping symptoms between CFS and MDD and performed an association study of the functional single-nucleotide polymorphism (SNP) in the DISC1 gene with CFS. Main methods: Venous blood was drawn from CFS patients and controls and genomic DNA was extracted from the whole blood according to standard procedures. Ser704Cys DISC1 SNP was genotyped using the TaqMan 5'-exonuclease allelic discrimination assay. Key findings: We found that the Cys704 allele of Ser704Cys SNP was associated with an increased risk of CFS development compared with the Ser704 allele. Significance: DISC1 Ser704Cys might be a functional variant that affects one of the mechanisms implicated in the biology of CFS. Some patients with CFS showed a phenotype similar to that of patients with MDD, but further studies are needed to clarify the biological mechanism, because this study is of a rather preliminary nature. Despite the variety of patients with CFS, DISC1 Ser704Cys has an association with CFS, which may also suggest that DISC1 plays a central role in the induction of various psychiatric diseases. © 2010 Elsevier Inc.

Miyata S.,Osaka University | Miyata S.,The Osaka Hamamatsu Joint Research Center For Child Mental Development | Koyama Y.,Osaka University | Takemoto K.,Osaka University | And 10 more authors.
PLoS ONE | Year: 2011

Repeated stressful events are known to be associated with onset of depression. Further, stress activates the hypothalamic-pituitary-adrenocortical (HPA) system by elevating plasma cortisol levels. However, little is known about the related downstream molecular pathway. In this study, by using repeated water-immersion and restraint stress (WIRS) as a stressor for mice, we attempted to elucidate the molecular pathway induced by elevated plasma corticosterone levels. We observed the following effects both, in vivo and in vitro: (1) repeated exposure to WIRS activates the 3-phosphoinositide-dependent protein kinase (PDK1)-serum glucocorticoid regulated kinase (SGK1)-N-myc downstream-regulated gene 1 (NDRG1)-adhesion molecule (i.e., N-cadherin, α-catenin, and β-catenin) stabilization pathway via an increase in plasma corticosterone levels; (2) the activation of this signaling pathway induces morphological changes in oligodendrocytes; and (3) after recovery from chronic stress, the abnormal arborization of oligodendrocytes and depression-like symptoms return to the control levels. Our data strongly suggest that these abnornalities of oligodendrocytes are possibly related to depression-like symptoms. © 2011 Miyata et al.

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