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Yuji Okazaki

Publications and source records attributed to Yuji Okazaki.

At least 19 recordsLinked to original sources
PubMed2007

Association study between the TNXB locus and schizophrenia in a Japanese population.

The chromosome 6p21-24 region, which contains the human leukocyte antigen (HLA) region, has been suggested as an important locus for a susceptibility gene for schizophrenia. Recently, a significant association between schizophrenia and the TNXB locus, located immediately telomeric of the NOTCH4 locus in the HLA region, was observed. Few studies have further investigated the region in schizophrenia. In the present study, we investigated the region in a Japanese population. Subjects included 241 patients with schizophrenia and 290 controls. Twenty-six single nucleotide polymorphisms (SNPs) and the corresponding haplotypes were analyzed. As a result, exactly the same SNPs in the TNXB locus (rs1009382 and rs204887) as in the previous study were associated with schizophrenia (P = 0.034 and 0.034, respectively, uncorrected). A SNP (rs2071287) in the NOTCH4 locus and haplotype around it were also suggested to associate with the disease, consistent with another previous study (P = 0.041 and permutation P = 0.024, respectively, uncorrected). Although these associations became insignificant after Bonferroni correction, the findings might provide support for the association of the TNXB locus or its adjacent region of the NOTCH4 locus with schizophrenia.

Adult↗
PubMed2007

Synaptotagmin XI as a candidate gene for susceptibility to schizophrenia.

Synaptotagmin XI (Syt11) is a member of the synaptotagmin family, which is localized in cells either in synaptic vesicles or the cellular membrane, and is known to act as a calcium sensor. The Syt11 gene is located on chromosome locus 1q21-q22, which was previously reported as a major susceptibility locus of familial schizophrenia. Here, we present evidence for an association between the number of 33-bp repeats in the promoter region of the Syt11 gene and schizophrenia. We found that the transcriptional activity of the gene is affected by the number of 33-bp repeats, which include an Sp1 binding site, suggesting that the excessive expression of Syt11 can be associated with schizophrenia. Another (single nucleotide) polymorphism in the Syt11 5'UTR region, where the potent transcription factor YY1 can bind, also affects the transcriptional activity of Syt11.

Base Sequence↗
PubMed2007

The correlation between unemployment and suicide rates in Japan between 1978 and 2004.

The number of suicides in Japan has increased from approximately 22,000 per year from 1988 to 1997 to over 30,000 per year since then; this increase is among the most important problems facing Japan. Moreover, the unemployment rate in Japan has increased rapidly since 1998. In this study, we examined the total number of suicides and both the suicide and unemployment rates in Japan from 1978 to 2004. We also focused on the correlation between annual suicide rates in Japan and the annual unemployment rates during the study period. During that period, 455,357 males and 225,012 females committed suicide in Japan, and the suicide rates by sex were 27.8 males and 13.3 females per 100,000 population (P<0.05). The annual suicide rates among males correlated significantly with the annual unemployment rates: r(27)=0.94, P<0.001, while the female suicide rates did not correlate with the unemployment rates: r(27)=0.39, P=0.05. Thus, when unemployed men are observed to be depressed, it is important for those close to them, as well as their health care professionals, to pay careful attention to their behavior to detect suicidal tendencies or intentions.

Female↗
PubMed2006

Suicidal tendencies among the elderly in Mie Prefecture, Japan, between 1996 and 2002.

This study aims to show the causative factors of suicide among the elderly (over 65) in Mie Prefecture, and to discuss the prevention of the factors contributing to suicide in the elderly group. We obtained an agreement from the Mie Prefectural Police Headquarters and investigated all inquest records collected between 1996 and 2002 in Mie Prefecture and focused on suicide in the elderly group. During the test period, the number of suicides in the elderly group was 842. In causative factors, the two major causative factors of suicide were "suffering from physical illness" and "psychiatric disorders". In particular, the three most frequent physical illnesses were "cardiovascular disease", "orthopedic disorder", and "digestive organ disease", and these physical illnesses are mentally stressful, and thus have a psychiatric component, the same as psychiatric illnesses do. Consequently, it is concluded that improvements in the home nursing and mental health care should include the prevention of suicide in the elderly who "suffer from physical illness" and "psychiatric disorders" to prevent suicide. In addition, medical staff and the general public should be educated on the factors that can influence elderly persons' mental condition, and should be cautioned to observe elderly persons for suicidal signs and symptoms.

Adult↗
PubMed2006

Haloperidol treatment induces tissue- and sex-specific changes in DNA methylation: a control study using rats.

BACKGROUND: We previously found that there is a subtle difference in the global methylation state of blood leukocyte DNA between male subjects with and without schizophrenia. The aim of the current study was to determine whether this difference was a primary effect of the disease state, or a secondary effect of antipsychotics administered to these patients. METHODS: We examined the methyl cytosine (mC) content of DNA from the leukocytes, brain, and liver of rats using high performance liquid chromatography. A total of 40 male and female rats received for 21 days daily injection of haloperidol or vehicle solution alone. RESULTS: In control rats injected with buffer only, there was a sex-dependent difference in mC content in leukocyte DNA (male > female; P = 0.028, n = 10), similar to our previous observations in human peripheral leukocytes. No difference in mC content between the sexes was observed in the brain or liver in buffer-treated animals. Haloperidol treatment slightly decreased the mC content of leukocytes in male rats, but unexpectedly, increased the mC content of leukocytes in females. We observed a trend toward a higher level of mC in the liver in both sexes following haloperidol treatment, compared to buffer-treated animals. In contrast, haloperidol treatment resulted in a decrease in mC content in the brain in females, and this difference was statistically significant (P = 0.026). CONCLUSION: These results indicate that haloperidol can affect DNA methylation states in the brain, as well as in certain other tissues, and raise the possibility that antipsychotic drugs play a role in the observed disparity in mC content in male subjects with and without schizophrenia.

Journal Article↗
PubMed2006

Global hypomethylation of peripheral leukocyte DNA in male patients with schizophrenia: a potential link between epigenetics and schizophrenia.

Genetic and epigenetic factors can potentially alter susceptibility to psychiatric disorders such as schizophrenia. In order to explore the effect of epigenetics on the pathogenesis of schizophrenia, we examined the global methylation level of leukocyte DNA from 210 patients with schizophrenia (124 males and 86 females) and 237 healthy subjects (108 males and 129 females). Methylated deoxycytidine (mC) content in peripheral leukocyte DNA was measured by high performance liquid chromatography (HPLC). We confirmed in the healthy subjects our previous finding that there are sex-dependent differences in mC content (males>females; beta=0.319, p<0.001), in addition to the effect of age (beta=-0.141, p=0.022). We therefore used multiple regression to analyze the data from all subjects by sex, with age as a co-variant. In males, a tendency was observed toward lower mC content in patients than in controls (beta=-0.115, p=0.075), with a significant effect of age (beta=-0.212, p<0.001). This difference was more prominent in younger individuals. In females, no effect of age or disease status on mC content was observed. These results established that there is significant sex-dependent difference in the mC content of human peripheral leukocyte DNA, and raise the possibility that alterations in DNA methylation state are present in patients with schizophrenia.

Adolescent↗
PubMed2006

No association between the metabotropic glutamate receptor type 3 gene (GRM3) and schizophrenia in a Japanese population.

Several lines of evidence have suggested that the metabotropic glutamate receptor 3 (GRM3) gene is a candidate susceptibility gene for schizophrenia. To our knowledge, six studies have investigated the genetic association between GRM3 and schizophrenia, although the results have been quite controversial. In the present study, we investigated the association between the GRM3 gene and schizophrenia in 402 Japanese people by analyzing 10 single nucleotide polymorphisms (SNPs), including all SNPs that showed significant results in previous studies. We observed no significant difference in allelic frequencies or genotypic distributions of the 10 SNPs between the controls and patients. A permutation test showed no significant global differences in estimated haplotype frequencies between the controls and patients. Thus, the present study provides no positive evidence of an association between the GRM3 gene and schizophrenia in the Japanese population.

Adult↗
PubMed2006

Association study of the dysbindin (DTNBP1) gene in schizophrenia from the Japanese population.

Dysbindin (DTNBP1: dystrobrevin binding protein 1), located on 6p22.3, is a candidate susceptibility gene for schizophrenia. Several studies, mostly in Caucasians, have provided evidence for an association between schizophrenia and the gene, although no common polymorphism or haploytpe has been established. In Asian populations, two studies investigated a limited number of single nucleotide polymorphisms (SNPs) of dysbindin and observed support for the association. In the present study, we investigated 12 SNPs of dysbindin, including those examined in previous Asian studies, and the corresponding haplotypes in a Japanese people with schizophrenia. As a result, no significant difference was observed between patients and controls in allelic frequencies or genotypic distributions of the 12 SNPs. Permutation test however showed significant differences in frequencies of the estimated 10-marker haplotypes between patients and controls (global p = 0.006). The present study may provide further support for an association between dysbindin and schizophrenia in Asian populations. The results might be similar to a previous Asian study, but specific haplotypes suggested for the association differed between the studies. Studies with more markers and subjects may be required before firm conclusions can be reached.

Adult↗
PubMed2006

Possible neuroleptic malignant syndrome related to concomitant treatment with paroxetine and alprazolam.

A 74-year-old man with depressive symptoms was admitted to a psychiatric hospital due to insomnia, loss of appetite, exhaustion, and agitation. Medical treatment was initiated at a daily dose of 20 mg paroxetine and 1.2 mg alprazolam. On the 10th day of paroxetine and alprazolam treatment, the patient exhibited marked psychomotor retardation, disorientation, and severe muscle rigidity with tremors. The patient had a fever (38.2 degrees C), fluctuating blood pressure (between 165/90 and 130/70 mg mm Hg), and severe extrapyramidal symptoms. Laboratory tests showed an elevation of creatine phosphokinase (2218 IU/L), aspartate aminotransferase (134 IU/L), alanine aminotransferase (78 IU/L), and BUN (27.9 mg/ml) levels. The patient received bromocriptine and diazepam to treat his symptoms. 7 days later, the fever disappeared and the patient's serum CPK levels were normalized (175 IU/L). This patient presented with symptoms of neuroleptic malignant syndrome (NMS), thus demonstrating that NMS-like symptoms can occur after combined paroxetine and alprazolam treatment. The adverse drug reaction score obtained by the Naranjo algorithm was 6 in our case, indicating a probable relationship between the patient's NMS-like adverse symptoms and the combined treatment used in this case. The involvement of physiologic and environmental aspects specific to this patient was suspected. Several risk factors for NMS should be noted in elderly depressive patients whose symptoms often include dehydration, agitation, malnutrition, and exhaustion. Careful therapeutic intervention is necessary in cases involving elderly patients who suffer from depression.

Aged↗
PubMed2006

Tissue specificity of methylation and expression of human genes coding for neuropeptides and their receptors, and of a human endogenous retrovirus K family.

The purpose of the present study was to understand the tissue specificity of DNA methylation and the relationship between methylation and expression of genes with essential roles in neurodevelopment and brain function. We chose dopamine receptor genes (DRD1 and DRD2), NCAM, and COMT as examples of genes with CpG islands around the promoter region, and serotonin receptor genes (HTR2A and HTR3A), HCRT, and DRD3 as genes without CpG islands. Methylation states were investigated in fetal brain, fetal liver, placenta, and in adult peripheral leukocytes from three individuals by Southern blot and bisulfite-modified DNA sequencing. A repetitive sequence, human endogenous retrovirus (HERV)-K was also examined. All genes examined were almost completely unmethylated in brains. The genes with CpG islands were unmethylated regardless of their expression state. In contrast, genes without CpG islands showed various methylation patterns, which did not necessarily reflect the transcriptional activity of the genes. Most HERV-K loci were methylated, but some loci showed relatively low methylation in the placenta and liver. Interestingly, we found inter-individual differences in methylation levels in HTR2A and HCRT in the placenta and in some loci of HERV-K in the placenta and liver. The sample with the lowest methylation levels in the two unique genes showed higher methylation of HERV-K loci than the other samples. These results provide detailed information about the methylation states of the genes analyzed and evidence for inter-individual variations in methylation in both unique and repetitive sequences.

Brain↗
PubMed2006

Effect of valine on the efficiency and precision at S4 cleavage of the Notch-1 transmembrane domain.

Presenilin-dependent intramembranous proteolysis mediates the dual cleavage of the Notch-1 protein (S4 and S3) as well as the beta amyloid precursor protein (betaAPP) (gamma40 and epsilon-site). betaAPP has a valine residue just before the gamma40 (amyloid beta [Abeta] numbering) site and after the epsilon-site. Both gamma40 and epsilon have multiple cleavage sites, and the varieties of gamma40 cleavage are associated with Alzheimer's disease (AD). These lines of evidence suggest that valine plays a role in the intramembranous proteolysis. S4 cleavage in the middle of the Notch-1 transmembrane domain (TMD) corresponds to the gamma40 cleavage of betaAPP. The cleavage site is in the center of four sequential alanine residues between Ala1731 and Ala1732, neither of which has a valine residue. To investigate the effects of valine on presenilin-dependent intramembranous proteolysis, we replaced the transmembrane domain residue of Notch-1 with valine and analyzed the efficiency and precision at S4 and S3. We observed that all valine-mutated Notch-1 proteins have a dominant cleavage site (S4) between Ala1731 and Ala1732 with some variations of cleavage precision, suggesting that valine is not indispensable for determining the cleavage site of the Notch-1 transmembrane domain, but affects the efficiency and precision at S4 cleavage of the Notch-1 transmembrane domain.

Amino Acid Sequence↗
PubMed2006

Causative factors as cues for addressing the rapid increase in suicide in Mie Prefecture, Japan: comparison of trends between 1996-2002 and 1989-1995.

The number of suicides in Japan has increased from approximately 22 000 per year from 1988 to 1997 to >30 000 per year since 1998. Likewise, the number of suicides has been increasing in Mie Prefecture. The purpose of the present study was to examine the incidence of and circumstances surrounding all suicide cases during 1996-2002 in Mie Prefecture and to compare the data with those from 1989 to 1995. In Mie Prefecture, the age-specific suicide rate during the second 7-year period included marked increases among men aged 50-59 and 60-69 years. Among women, the age-specific suicide rate increased with age during both 7-year periods. During the second period, psychiatric disorders as causative factors increased in all generations. They were especially important for women of the younger generation, whereas economic problems were the most common causative factor among men aged 40-64. Physical illness as a causative factor in suicide was high among the elderly, but among the other age groups this factor trailed behind economic difficulties for men and psychiatric disorders for women. To prevent suicide, social cooperation as well as a plenitude of visiting nurses and psychiatric care is required, and early detection and treatment are also important.

Adult↗