Biomedical subjects

Tadashi Umekage

Publications and source records attributed to Tadashi Umekage.

At least 19 recordsLinked to original sources

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

Insertional polymorphism of endogenous retrovirus HERV-K115 in schizophrenia.

Retroviruses are implicated in the pathogenesis of schizophrenia. Human endogenous retrovirus type K115 (HERV-K115) is a full-length, potentially transcriptional retrovirus and is also polymorphic. We investigated the frequency of HERV-K115 in Japanese schizophrenia patients and healthy controls. No difference was found in the frequency between patients and controls (8.4% versus 9.4%, respectively). However, a marginal difference was observed in age at onset between the HERV-K positive and negative patients (p=0.057). The HERV-K115 insertion appeared to be more frequent in patients with younger onset than those with later onset. These results preliminarily suggest that HERV-K115 may not be associated with schizophrenia in general, but that it could play a partial role in early precipitation of the disease.

Adult↗

PubMed2006

No association between the Clara cell secretory protein (CC16) gene polymorphism and personality traits.

Clara cell secretory protein (CC16) is an anti-inflammatory protein expressed in the respiratory tract. Several studies have suggested the association between CC16 and mental disturbances, such as schizophrenia, depression, and post-traumatic stress disorder. In the present study, we investigated the association between the CC16 gene A38G polymorphism and personality traits in 214 healthy Japanese subjects. Personality traits were evaluated by using the Revised NEO Personality Inventory (NEO PI-R) and the State-Trait Anxiety Inventory (STAI). As a result, no significant association was observed between the genotypes and the scores of the NEO PI-R or the STAI. The present results suggest that CC16 may not have a major role in the development of personality traits.

Adult↗

PubMed2006

Association of mitochondrial complex I subunit gene NDUFV2 at 18p11 with schizophrenia in the Japanese population.

Schizophrenia and bipolar disorder share common genetic background. Several loci such as 18p11, 13q32, and 22q11-13 were commonly linked with these diseases. Since mitochondrial dysfunction has been suggested in both of these disorders, NDUFV2 at 18p11, encoding a subunit of the complex I, NADH ubiquinone oxidoreductase, is a candidate gene for these diseases. We previously reported that single nucleotide polymorphisms (SNPs) in the upstream region of NDUFV2 were associated with bipolar disorder in Japanese. The association of haplotype consisting of two SNPs, -3542G > A and -602G > A, with bipolar disorder was also seen both in Japanese and the National Institute of Mental Health Pedigrees trios. In this study, 2 polymorphisms, -3542G > A and -602G > A, were investigated in 229 schizophrenic patients as compared with controls. Individual genotypes were not associated with schizophrenia. However, the haplotype consisting of these two SNPs were significantly associated with schizophrenia. These results suggested that inter-individual variation of the genomic sequence of the promoter region of NDUFV2 might be a genetic risk factor common to bipolar disorder and schizophrenia.

Adult↗

PubMed2006

Association between dopamine D4 receptor (DRD4) exon III polymorphism and Neuroticism in the Japanese population.

The association between the dopamine D4 receptor (DRD4) exon III polymorphism and personality trait of novelty seeking (NS) has been studied intensively. In the Japanese population, the results of the previous studies did not always coincide. In the present study, we investigated the association between the polymorphism and personality traits evaluated by using the Revised NEO Personality Inventory (NEO PI-R) and State-Trait Anxiety Inventory (STAI) in 196 Japanese subjects. A meta-analysis of the present and previous Japanese studies was also conducted regarding NS. As a result, significant association was observed between the polymorphism and personality traits evaluated by using NEO PI-R as a whole (p=0.022, MANCOVA). Subsequent analyses showed a significant association between short alleles (2-4 repeats) and higher scores for Neuroticism or its subscales, Anxiety, Depression, and Vulnerability (p=0.015, 0.039, 0.021, and 0.008, respectively, uncorrected). No other significant difference in the scores for NEO PI-R was observed in the subsequent analyses. Significant association was also observed between the polymorphism and scores for STAI as a whole (p=0.004, MANCOVA). Subsequent analyses did not show significant association, although a weak trend for the relation between the genotype consisting of short alleles and Trait Anxiety was observed (p=0.10, uncorrected). The meta-analysis showed no significant association between the polymorphism and NS. Thus, the present study suggested the association between the short allele of the DRD4 exon III polymorphism and personality trait of Neuroticism in Japanese subjects.

Adult↗

PubMed2006

No association between the CNTF null mutation and schizophrenia or personality.

The ciliary neurotrophic factor (CNTF) is a neurotrophic cytokine that plays a critical role in neurodevelopment. On the basis of neurodevelopmental hypothesis, the CNTF gene has been a candidate locus for schizophrenia. Several studies have investigated the association between the null mutation of the gene and schizophrenia, however, with inconsistent results. In the present study, we investigated the association in 222 Japanese patients with schizophrenia and 237 controls. The association between the mutation and personality traits was also studied, to investigate the effect of the mutation in participants from the general population. As a result, no association was observed between the mutation and schizophrenia nor personality traits, evaluated by using the Revised NEO Personality Inventory scores. The present study did not provide evidence for the association between the CNTF gene and schizophrenia or personality traits in the Japanese population.

Alleles↗

PubMed2006

Association between corticotropin-releasing hormone receptor 2 (CRHR2) gene polymorphism and personality traits.

Corticotropin-releasing hormone (CRH) has been implicated in the pathophysiology of anxiety disorders and depression. Corticotropin-releasing hormone receptor 2 (CRHR2) is one of the receptors that mediate CRH signal. The purpose of the present study was to investigate the association between the CRHR2 gene and personality traits, evaluated using the Revised NEO Personality Inventory (NEO PI-R), in 243 healthy Japanese subjects. As a result, significant association was observed between the polymorphism in intron 2 (rs2267717) and Openness (P = 0.004, uncorrected, anova), while no relationship was observed concerning Neuroticism. The present result suggests an association between CRHR2 and the personality trait of Openness.

Adult↗

PubMed2005

Combined analysis of association between personality traits and three functional polymorphisms in the tyrosine hydroxylase, monoamine oxidase A, and catechol-O-methyltransferase genes.

Several molecular genetic studies have been conducted with regard to the association between catecholamine-related genes and personality traits. However, the results of replication studies did not always coincide. One of the possible reasons may be that the effect exerted by the individual gene is small. In the present study, we investigated the association between personality traits and systematic combination of functional polymorphisms in three genes that regulate the metabolism of catecholamines, namely, tyrosine hydroxylase (TH), monoamine oxidase A (MAOA), and catechol-O-methyltransferase (COMT). The (TCAT)n repeat in the TH gene, the promoter variable number tandem repeat (VNTR) in the MAOA gene, and Val158Met in the COMT gene were genotyped in 256 healthy Japanese volunteers. Personality traits were evaluated using the NEO Personality Inventory-Revised (NEO PI-R). As a result, the score for Neuroticism increased, and those for Extraversion and Conscientiousness decreased according to the degree of functional polymorphic change, i.e., the lower synthesis/higher catalysis of catecholamines. A statistically significant difference was observed in the change of Extraversion (p=0.04, after Bonferroni correction). These results may provide evidence for the association between metabolic change of catecholamines and personality traits, which may be due to the additive effect of the three genes.

Adult↗

PubMed2005

Functional polymorphisms of HSPA5: possible association with bipolar disorder.

Altered endoplasmic reticulum stress (ER) response signaling is suggested in bipolar disorder. Previously, we preliminarily reported the genetic association of HSPA5 (GRP78/BiP) with bipolar disorder. Here, we extended our analysis by increasing the number of Japanese case-control samples and NIMH Genetics Initiative bipolar trio samples (NIMH trios), and also analyzed schizophrenia samples. In Japanese, nominally significant association of one haplotype was observed in extended samples of bipolar disorder but not in schizophrenia. In NIMH trios, no association was found in total samples. However, an exploratory analysis suggested that the other haplotype was significantly over-transmitted to probands only from the paternal side. The associated haplotype in Japanese or NIMH pedigrees shared three common polymorphisms in the promotor, which was found to alter promotor activity. These findings suggested promotor polymorphisms of HSPA5 may affect the interindividual variability of ER stress response and may confer a genetic risk factor for bipolar disorder.

Adult↗

PubMed2005

XBP1 gene polymorphism (-116C/G) and personality.

Recently, a polymorphism of the XBP1 gene (-116 C/G) was observed to play a significant role in the development of bipolar mood disorder from the Japanese population. The present study investigated a role of the polymorphism in the development of personality in healthy Japanese volunteers (n = 195). Personality traits were evaluated using NEO Personality Inventory-Revised (NEO PI-R). As a result, a statistical trend for association between the polymorphism (genotype) and the NEO PI-R scores of agreeableness and neuroticism was observed (ANOVA, P = 0.01 and 0.006, respectively). Subjects with the G allele, especially those with G-G genotype, tended to show lower neuroticism and higher agreeableness in the present study. The result is provisional and should be interpreted with caution, partly because the previous study suggested the allele as a risk allele for bipolar disorder. Further studies are required to confirm the results.

Adult↗

PubMed2005

Seasonality of schizophrenia births in the Japanese population: increased winter births possibly confined to the north area.

A number of North American and European studies have observed a higher proportion of winter births in schizophrenia patients. Thus, seasonal fluctuation of unknown environmental factors may affect brain development in ways that alter susceptibility to schizophrenia. Specification of these factors may help elucidate the etiopathological mechanism of the disease, about which little is certain. A small number of studies have investigated this issue in Asian populations, and the findings are not as consistent as those of Western populations. No remarkable excess of winter births has been observed in Japanese or Korean studies, while some studies have reported a significant decrease of summer births. We further investigated the issue in Japanese patients with schizophrenia (n=3927). No significant excess of winter births was observed, but a decrease in the summer births was found in male subjects. This is largely consistent with previous Japanese studies; however, when the subjects were confined to those born in a colder and higher latitude area of Japan (n=1338), a consistent trend for both a winter increase, and a summer decrease, was found. However, the results did not consistently reach statistical significance, possibly due to the lack of statistical power. Environmental factors that correlate with latitude might play a role in the development of the seasonality of births in schizophrenia. Further studies in a larger sample size are required to test these possibilities.

Catchment Area, Health↗

PubMed2005

Serotonin 2A receptor gene polymorphism and personality traits: no evidence for significant association.

A number of studies have observed associations between the serotonin 2A (5-HT2A) receptor and mental disorders. Here, we investigated correlations between polymorphisms (-1438G/A and 102T/C) of the 5-HT2A gene and personality traits in healthy Japanese volunteers (n = 239). The personality traits were evaluated using the Revised NEO Personality Inventory (NEO PI-R). The -1438G/A and 102T/C were in complete linkage disequilibrium. There was a tendency for associations between the genotype and the scores for Agreeableness, Conscientiousness and Neuroticism of the NEO PI-R (P = 0.028, 0.039 and 0.062, respectively; analysis of variance, uncorrected for multiple testing). Subjects with the A/A of -1438G/A (or T/T of 102T/C) appeared to be lower in Neuroticism and higher in Conscientiousness than the rest of the subjects. However, the results were statistically non-significant after Bonferroni's correction for multiple testing of the five scales of the NEO PI-R. Thus, the present study provided no evidence for statistically significant associations between the 5-HT2A polymorphisms and the personality traits.

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

Mitochondrial DNA sequence analysis of patients with 'atypical psychosis'.

Although classical psychopathological studies have shown the presence of an independent diagnostic category, 'atypical psychosis', most psychotic patients are currently classified into two major diagnostic categories, schizophrenia and bipolar disorder, by the Diagnostic and Statistical Manual of Mental Disorders (4th edn; DSM-IV) criteria. 'Atypical psychosis' is characterized by acute confusion without systematic delusion, emotional instability, and psychomotor excitement or stupor. Such clinical features resemble those seen in organic mental syndrome, and differential diagnosis is often difficult. Because patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) sometimes show organic mental disorder, 'atypical psychosis' may be caused by mutations of mitochondrial DNA (mtDNA) in some patients. In the present study whole mtDNA was sequenced for seven patients with various psychotic disorders, who could be categorized as 'atypical psychosis'. None of them had known mtDNA mutations pathogenic for mitochondrial encephalopathy. Two of seven patients belonged to a subhaplogroup F1b1a with low frequency. These results did not support the hypothesis that clinical presentation of some patients with 'atypical psychosis' is a reflection of subclinical mitochondrial encephalopathy. However, the subhaplogroup F1b1a may be a good target for association study of 'atypical psychosis'.

Aged↗

PubMed2004

Association between the neurofibromatosis-1 (NF1) locus and autism in the Japanese population.

Autistic patients have a 100 to 190-fold increased risk of neurofibromatosis compared to the general population. This suggests that the two diseases may share a common etiological background. Recently, a new allele (or the six-repeat allele) of the (AAAT)(n) repeat polymorphism in an Alu sequence in the neurofibromatosis-1 (NF1) gene was observed exclusively in severe autistic patients, not in controls, in Caucasians of French ancestry. This suggests a role of the NF1 gene in the development of autism. We investigated three microsatellite polymorphisms within the intron-27b and intron-38 of the NF1 region, including the (AAAT)(n) and two (CA)n repeat polymorphisms, in Japanese subjects with autism (n = 74) and controls (n = 122). The six-repeat allele of the (AAAT)(n) polymorphism was not found either in patients or controls, possibly indicating an ethnic difference in the polymorphism. However, significant differences were observed in the allele distributions of the (AAAT)(n) and a (CA)(n), which were located at intron-27b, between patients and controls, although an association was not significant between autism and another polymorphism at intron-38. This may suggest an involvement of the NF1 locus in susceptibility to autism, although further investigations are recommended.

Adolescent↗

PubMed2004

Season of birth effect on personality in a general population.

Seasonality of births in schizophrenia and other mental disorders has been consistently observed. This may be through effects of unknown environmental factors that seasonally fluctuate on the brain development. The effects may affect cognitive function of the brain and behavioral characteristics that might be correlated with the development of personality not only in patients with mental disorders but also in healthy subjects. We, therefore, investigated the effects of season of birth on personality traits in healthy Japanese adults (n = 397). Personality traits were evaluated using the NEO Personality Inventory-Revised (NEO PI-R). A trend for lower Agreeableness in subjects born during winter (December to February) than other subjects was observed (P = 0.036, after correction for the multiple testing, multiple regression analysis adjusting for age and sex). Other major factors of the NEO PI-R, including Neuroticism, Extraversion, Openness and Conscientiousness, were not affected by season of birth. Further studies may be recommended to confirm the results, considering the relatively limited sample size. Evaluation of cognitive functions and behaviors using other measures including event-related potentials and functional MRI may also help the interpretation of the present result.

Adult↗

PubMed2004

Mitochondrial DNA polymorphisms and extraversion.

Mitochondria is the major site of energy production in cells, therefore, mitochondrial abnormality may affect functions of organs including the brain, which constantly requires high levels of energy consumption. Previous studies have suggested a role of mitochondria and their DNA polymorphisms in neuro-psychiatric disorders, including Alzheimer's disease, Parkinson's disease, schizophrenia and bipolar mood disorder. Thus, we hypothesized that mitochondrial DNA polymorphisms might be related with the development of personality. The present study investigated a role of two mitochondrial DNA polymorphisms, the C5178A and A10398G, in personality traits evaluated using the NEO PI-R scores in 238 healthy Japanese volunteers. Subjects with the 5178A genotype showed significantly higher extraversion score than those with the 5178C genotype (P = 0.027), while no significant association was observed between the C5178A polymorphism and other scores. No significant association was found between the A10398G polymorphism and any scores. Regarding the 5178-10398 haplotype, the score of extraversion, not other scores, was significantly associated with the A-G haplotype (P = 0.042). Although further studies are recommended for the confirmation, the result may suggest a role of the mitochondrial DNA polymorphism in the personality trait.

Adult↗

PubMed2004

Association of six polymorphisms of the NOTCH4 gene with schizophrenia in the Japanese population.

The NOTCH4 gene is located at 6p21.3 and involved in the development and patterning of the central nervous systems. Recently, Wei and Hemmings [2000] observed that the gene was associated with schizophrenia. Subsequent to the report, several studies investigated the gene in schizophrenia, with controversial and inconclusive results. In the present study, we investigated six polymorphisms (SNPs 1-5 and a CTG repeat) of the gene in Japanese subjects with schizophrenia (n = 284) and the same number of controls. The polymorphisms include SNP5, which has been observed to be associated with schizophrenia in a Chinese population and two new SNPs 3-4 adjacent to SNP5, in addition to the SNPs 1-2 and the CTG repeat, which were suggested for the association with the disease in the previous study. As a result, no significant difference in genotypic distributions or allelic frequencies of the six polymorphisms of the gene was observed between the patients and the controls. Also, no significant difference was found in frequencies of haplotypes of the six polymorphisms between the patients and the controls. However, the distribution of SNP2 was significantly deviated from Hardy-Weinberg equilibrium in the patients (P = 0.000986), not in the controls, which could be a chance or due to an association of SNP2 with the disease. In conclusion, the present study provided no clear evidence for an association between the NOTCH4 gene and schizophrenia in the Japanese population.

Adult↗