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Yuji Okazaki

Publications and source records attributed to Yuji Okazaki.

At least 37 records · Page 2Linked to original sources
PubMed2005

Genomewide high-density SNP linkage analysis of 236 Japanese families supports the existence of schizophrenia susceptibility loci on chromosomes 1p, 14q, and 20p.

The Japanese Schizophrenia Sib-Pair Linkage Group (JSSLG) is a multisite collaborative study group that was organized to create a national resource for affected sib pair (ASP) studies of schizophrenia in Japan. We used a high-density single-nucleotide-polymorphism (SNP) genotyping assay, the Illumina BeadArray linkage mapping panel (version 4) comprising 5,861 SNPs, to perform a genomewide linkage analysis of JSSLG samples comprising 236 Japanese families with 268 nonindependent ASPs with schizophrenia. All subjects were Japanese. Among these families, 122 families comprised the same subjects analyzed with short tandem repeat markers. All the probands and their siblings, with the exception of seven siblings with schizoaffective disorder, had schizophrenia. After excluding SNPs with high linkage disequilibrium, we found significant evidence of linkage of schizophrenia to chromosome 1p21.2-1p13.2 (LOD=3.39) and suggestive evidence of linkage to 14q11.2 (LOD=2.87), 14q11.2-q13.2 (LOD=2.33), and 20p12.1-p11.2 (LOD=2.33). Although linkage to these regions has received little attention, these regions are included in or partially overlap the 10 regions reported by Lewis et al. that passed the two aggregate criteria of a meta-analysis. Results of the present study--which, to our knowledge, is the first genomewide analysis of schizophrenia in ASPs of a single Asian ethnicity that is comparable to the analyses done of ASPs of European descent--indicate the existence of schizophrenia susceptibility loci that are common to different ethnic groups but that likely have different ethnicity-specific effects.

Chromosomes, Human, Pair 1↗
PubMed2005

Association study of the DISC1/TRAX locus with schizophrenia in a Japanese population.

Disrupted-in-Schizophrenia-1 (DISC1), identified by cytogenetic approaches in a pedigree with familial psychosis, is considered a candidate susceptibility gene for schizophrenia in some populations. In the pedigree, the TRAX gene, located adjacent to DISC1 on the disrupted chromosome 1, may also contribute to the pathophysiology of the familial schizophrenia. We studied association of the DISC1 and TRAX genes with schizophrenia in 338 Japanese by analyzing 15 single nucleotide polymorphisms (SNPs), including 12 SNPs in DISC1 and three in TRAX, respectively. No significant difference was observed between the patients and controls in allelic frequencies or genotypic distributions of 15 SNPs. A weak trend for the association in genotypic distribution of one SNP in TRAX (major homo/hetero/minor homo: 0.324/0.431/0.245 vs. 0.293/0.526/0.181 for patients vs controls, p = 0.039 in the 2 x 3 comparison) turned out to be insignificant after Bonferroni correction. Haplotype analysis did not support the association between the patients and controls. The present study suggests that the DISC1/TRAX locus may not have a major role in Japanese schizophrenia.

Adult↗
PubMed2005

Factors associated with the development of panic attack and panic disorder: survey in the Japanese population.

Environmental factors, in addition to genetic factors, may be related to the development of panic attack (PA) and panic disorder (PD). Previous studies suggested that there may be seasonal variation in the onset of PA/PD and possibly a higher prevalence of PA/PD in colder areas. Also observed were lactate-induced PA and elevated serum cholesterol in PD patients. These suggest that living environment and lifestyle, such as weather conditions, preference of food and physical exercise, might play a role in the occurrence of PA and PD. The present study explored the association of such candidate factors with the development of PA and PD in 4000 Japanese subjects, using a questionnaire. The subjects were recruited from the general population of Japan, using stratified random sampling. Logistic regression with stepwise selection of variables was employed for statistical analysis. Variables including "dislike of physical exercise", mostly in female subjects, and "living in areas with longer winter", in male subjects, were suggested for associations with PA and PD among the candidate factors. The result is preliminary but indicates that lifestyle such as like/dislike of physical exercise and environmental factors including weather conditions could play a partial role in the development of PA and PD. Further investigations are required before firm conclusions can be reached.

Adaptation, Psychological↗
PubMed2005

Underlying factors for the rapid increase of suicide in Mie Prefecture, Japan.

The number of suicides in Japan increased from about 22,000 per year during the period 1988 to 1997 to over 30,000 since 1998. The number of suicides has also been increasing in Mie Prefecture. In the present study we examined the incidence and the circumstances for all suicidal cases during the seven-year period, 1996-2002, that were reported to Mie Prefectural Police Headquarters. In Mie Prefecture, the number of suicides per year averaged 421 cases: from a minimum of 319 in 1997 to a maximum of 501 in 1998. The most frequent month for suicides was July, while the lowest number occurred in February. Suicide was most common in the 50-59 year age group in men, and in the 70-79 year group in women. Regarding the means of suicide, hanging was the most frequent (61.6%) in both sexes. Psychiatric disorders were the most serious causative factors in all generations, accounting for 23.8% in general but being especially prevalent in the younger generation of people under 39 years. Further reasons for suicide were economic problems for the 40-64 age-group in men and suffering from illness for the elderly age-groups in both sexes. In order to prevent suicide, urgent strategies for effective medical treatments and improved working circumstances are required.

Adult↗
PubMed2004

What causes seasonality of birth in schizophrenia?

An excess of winter-spring births (and/or a decrease of summer births) has consistently been observed in schizophrenia (SCZ). This observation may provide a significant clue about the causes of the disease if specific factors which cause the phenomenon can be determined. This paper reviews several studies which investigated factors correlated with this observation in SCZ, in an attempt to determine which factors more likely cause the seasonality. Among the candidates of the factors are meteorological variables (such as ambient temperature), several infections, maternal hormones, sperm quality, nutrition and external toxins. A variation of procreation might also have an effect. Among the factors, the most extensively studied are temperature and viral infections. Some of them have appeared promising, but further studies are definitely required. Several challenges, including complicated correlations of the factors and determination of the susceptible period during pregnancy, need to be overcome. Comparisons of the data from areas and cohorts with different patterns of the candidate factors may be helpful. Animal studies may also help investigate the molecular and physiological mechanisms of the phenomenon.

Animals↗
PubMed2004

Characteristics of a Japanese adult twin database of high school graduates.

This paper profiles a unique cohort of adult Japanese twins. The database contains more than 700 twin pairs, aged 18 to 66 years, who are all graduates of the secondary school attached to the faculty of education of the University of Tokyo. This school was established in 1948, when the study of twins was burgeoning in Japan, and about 10 to 20 pairs of twins have been admitted there every year to participate in studies on twins in education and in related projects. The zygosity of all twins was determined carefully on the basis of various sources. Data from the perinatal period to adulthood were linkable using ID numbers. Follow-up surveys in the field of medical genetics were performed in 1985, 1989 and 1999. For the third survey, which was sent and received exclusively by mail, the distribution and collection process was also assessed in detail. The response rate was around 40%, which statistically was influenced mainly by previous participation and sex. The limitation of this cohort is its selection bias concerning socioeconomic status and its imbalance in favor of monozygotic pairs.

Adolescent↗
PubMed2003

Polymorphic 33-bp repeats with promoter-like activity in synaptotagmin 11 gene.

In the immediate upstream region of the transcription initiation site of human synaptotagmin 11 gene, we found a tandem repeat of a 33-bp unit with a promoter-like activity. The tandem repeat is apparently polymorphic in the Japanese population as two DNA samples from 60 schizophrenia patients exhibited an increased number (three) of the unit. In a transfection assay using constructs with different numbers of repeats, the promoter-like activity was found to increase with the number of repeating unit.

Animals↗
PubMed2003

Human endogenous retroviruses with transcriptional potential in the brain.

Genetic studies of neuropsychiatric disorders have often produced conflicting results, which might partly result from the involvement of epigenetic modifications. We intended to explore the possible implication of DNA methylation and human endogenous retroviruses (HERVs) in neuropsychiatric disorders. In the present study, we identified two HERV loci that are expected to retain the transcriptional activity in the brain. One was located on chromosome 1q21-q22 and the other on 22q12. Interestingly, these regions were overlapped with or included in those of schizophrenia-susceptible loci, SCZD9 and SCZD4, respectively. Particularly, the HERV on 22q12 was located in the opposite direction 4 kb downstream of the Synapsin III gene. These HERV loci could afford clear targets for methylation and expression analyses in postmortem brains of patients with psychiatric disorders such as schizophrenia. In addition, we confirmed our previous finding that only a few of particular HERV-K loci were activated among a number of highly homologous loci in teratocarcinoma cell lines. These activated loci included ones common to all teratocarcinoma cell lines analyzed and depending on their male or female origin.

Brain↗
PubMed2003

Impaired feedback regulation of XBP1 as a genetic risk factor for bipolar disorder.

The pathophysiology of bipolar disorder is still unclear, although family, twin and linkage studies implicate genetic factors. Here we identified XBP1, a pivotal gene in the endoplasmic reticulum (ER) stress response, as contributing to the genetic risk factor for bipolar disorder. Using DNA microarray analysis of lymphoblastoid cells derived from two pairs of twins discordant with respect to the illness, we found downregulated expression of genes related to ER stress response in both affected twins. A polymorphism (-116C-->G) in the promoter region of XBP1, affecting the putative binding site of XBP1, was significantly more common in Japanese patients (odds ratio = 4.6) and overtransmitted to affected offspring in trio samples of the NIMH Bipolar Disorder Genetics Initiative. XBP1-dependent transcription activity of the -116G allele was lower than that of the -116C allele, and in the cells with the G allele, induction of XBP1 expression after ER stress was markedly reduced. Valproate, one of three mood stabilizers, rescued the impaired response by inducing ATF6, the gene upstream of XBP1. These results indicate that the -116C-->G polymorphism in XBP1 causes an impairment of its positive feedback system and increases the risk of bipolar disorder.

Base Sequence↗
PubMed2003

Effects of single and repeated prolonged stress on mu-opioid receptor mRNA expression in rat gross hypothalamic and midbrain homogenates.

This study tested the hypothesis that stress-induced opioid peptides may have stimulative and inhibitive influence on mu opioid receptor (MOR) mRNA expression and hypothalamus. Several studies have investigated the effects of stress on MOR mRNA expression in rat brain, but almost none compared the response to single versus repeated stresses. Here, we examined the effects of single and repeated stress on MOR mRNA expression in different rat brain regions using reverse transcriptase-polymerase chain reaction (RT-PCR). Following a single episode of restraint stress for 4 h (1R) or 4 h per day on 2 (2R) or 3 (3R) consecutive days, the hypothalamus and midbrain were removed immediately and MOR mRNA levels in both regions were determined by RT-PCR. Blood samples were also collected for simultaneous measurement of serum adrenocorticotropic hormone (ACTH) and corticosterone (CS). MOR mRNA expression was significantly higher in both regions in the 2R group, whereas expression levels in the 3R group did not differ from controls. In the 1R group, hypothalamic MOR expression was equivalent to that in controls, but expression was significantly higher in the midbrain. Serum ACTH levels were significantly higher only in the 1R group, whereas serum CS was significantly higher in both the 1R and 3R groups. Our findings indicate that the influence of restraint stress on MOR mRNA expression in the hypothalamus is different than in the midbrain region in rats. Endogenous opioid peptides released in response to stress may paradoxically have an effect on the HPA axis.

Animals↗
PubMed2003

Increased expression of corticotropin-releasing factor receptor mRNA in the locus coeruleus of stress-induced rat model of depression.

Hypersecretion of corticotropin-releasing factor (CRF) has been hypothesized to occur in depression. To investigate CRF receptor (CRFR) response to the increased production of CRF in chronically stressed rats, we measured by in situ hybridization the expression of CRFR mRNA in the locus coeruleus (LC) concomitant with measuring plasma adrenocorticotropin (ACTH). The expression of both CRFR mRNA in the LC and the plasma level of ACTH increased significantly in "depression-model rats" which exhibit reduced activity following exposure to 14 days forced walking stress (FWS), but not in "spontaneous recovery rats" whose activity was restored after the long-term stress. These results suggest that the LC neurons continue to be stimulated by CRF, and that the hypothalamic-pituitary-adrenal (HPA) axis is hyperfunctioning in the depression-model rats.

Adrenocorticotropic Hormone↗
PubMed2003

Effects of odorants on the hypothalamic-pituitary-adrenal axis and interleukin-6 (IL-6) and IL-6 receptor mRNA expression in rat hypothalamus after restraint stress.

We recently reported that stress alters interleukin (IL)-6 and IL-6 receptor (IL-6R) mRNA levels in the hypothalamus. Odorants are reported to exert anti-stress effects. The aim of our study was to determine the effects of odorants on IL-6 and IL-6R mRNA expression in the hypothalamus, using reverse transcriptase-polymerase chain reaction and on serum levels of adrenocorticotropic hormone (ACTH) and corticosterone in rats exposed to stress. Control rats were not exposed to stress; test control rats were exposed to 4 h stress then immediately killed. In other groups, rats were exposed to the same stress followed by 30 min exposure air, dimethoxymethylbenzene (DMMB), or citralva. In the air group, IL-6 and IL-6R mRNA levels were significantly reduced and serum levels of ACTH and corticosterone significantly increased relative to the control. Exposure to DMMB significantly augmented IL-6 mRNA expression but restored that of IL-6R mRNA, did not change serum corticosterone level relative to that of the air group and significantly reduced ACTH. In comparison, citralva restored the expression of IL-6 and IL-6R mRNAs and significantly increased serum ACTH and corticosterone levels. Our results indicate that citralva enhances stress-induced activation of the hypothalamic-pituitary-adrenal axis by corticotropin-releasing hormone (CRH)-mediated stimulation of IL-6, while DMMB enhances the beneficial action of IL-6 without affecting CRH.

Animals↗
PubMed2002

HLA class I distribution in Japanese patients with schizophrenia.

Several Caucasian studies and one Japanese study have observed associations between human leukocyte antigen (HLA) class I specificities, including A24 (9) and A26 (10) and schizophrenia. Most of those studies were conducted in 1970s and early 1980s, when the typing technique of HLA was not adequately reliable. Also, an operational diagnostic system was not employed in many of the studies. The present study investigated frequencies of HLA-A specificities in schizophrenia patients (ICD-10 and DSM-III-R, n=98) and sex-matched healthy controls (n=392) from population in the southwestern part of Japan. HLA-B and -C specificities were studied in addition. Frequencies of subjects possessing A24 and A26 were not different between the patients and controls (54% and 24% in the patients and 62% and 24% in the controls, respectively). No significant difference was found in frequencies of other class I (A, B, and C) specificities between the patients and the controls. Thus, the present study provided no evidence for an association between the HLA class I specificities, including A24, A26, and others, and schizophrenia in the Japanese population.

Adult↗
PubMed2002

Late-onset depression: can EEG abnormalities help in clinical sub-typing?

BACKGROUND: The purpose of this study was to determine the frequency of EEG abnormalities indicative of mild cerebrovascular dysfunction in patients with late-onset depression and to correlate these abnormalities with clinical features. METHODS: The subjects, aged > or = 50 years, were 51 outpatients with major depression diagnosed according to DSM-IV criteria. They were living in the community and prospectively selected at their initial consultation for mostly mild-moderate depression. We also included 32 normal age-matched controls. We examined basic rhythms and temporal slow waves on EEG and determined the Hamilton Rating Scale for Depression (HAMD) as a scale for the severity of psychiatric symptoms. RESULTS: Temporal slow waves were more common in depressed patients (47%) than in normal controls (22%). Depressed patients with temporal slow waves had significantly lower frequency of family history of mood disorders (P<0.05). There was no difference in the total score of HAMD between patients with and without temporal slow waves, however, each score of HAMD in patients with temporal slow waves showed a significantly lower score for "feeling of guilt" (P<0.01) and a significantly higher score for "general somatic symptoms" (P<0.01) and "hypochondriasis" (P<0.01). CONCLUSIONS: Our EEG study suggested that temporal slow waves, which were probably associated with subtle cerebrovascular lesions, might reflect vulnerability to late-onset depression. In addition, depressed patients with temporal slow waves could be classified as a subgroup of heterogeneous late-onset depression based on the clinical findings. These results must be interpreted within the limitations of the sample selection procedure.

Age of Onset↗
PubMed2002

Molecular genetic studies of schizophrenia: challenges and insights.

Schizophrenia (SCZ) is a mental disease that affects approximately 1% of the population with life-long devastating consequences. Based on evidence for a major contribution of genetic factors, a decade of extensive efforts has been dedicated to the search of DNA sequence variations that increase the risk to SCZ. Search for genes in rare multiplex SCZ families with a large number of affected individuals and quasi-Mendelian mode of inheritance using genetic linkage methodology has been one of the favorite strategies in psychiatric genetics. Although several genomic regions were suggested for linkage to SCZ, not a single gene causing or predisposing to SCZ has been identified thus far. Furthermore, it is not clear whether the genes of familial SCZ are also involved in sporadic cases that represent the overwhelming majority of SCZ patients. For sporadic cases, genetic association studies comparing the distribution of allelic frequencies of candidate genes in SCZ patients and controls have been performed but the outcome of such studies has also been quite modest. Several factors such as possible involvement of numerous interactive genes of minor effect, yet unknown environmental effects and diagnostic ambiguities of the disease have made genetic studies in SCZ quite unproductive. In terms of future studies, a genome-wide association search is a promising approach; however, this approach requires genotyping of thousands of genetic markers in large samples. In addition, a detailed analysis of the genes, expression of which changes under the influence of environmental factors, can indicate good candidates for genetic association studies. In this connection, investigations of the epigenetic regulation of genes and not only the DNA sequence variation, may be necessary for complete understanding of the etiopathogenic mechanisms of SCZ.

Environment↗