Biomedical subjects

Mamoru Tochigi

Publications and source records attributed to Mamoru Tochigi.

11 recordsLinked to original sources

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↗

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

Gastrin-releasing peptide receptor (GRPR) locus in Japanese subjects with autism.

Gastrin-releasing peptide receptor (GRPR) gene is considered a candidate locus for infantile autism for several reasons. The present study investigated two polymorphic sites (C/450/T and C/661/T) in the second exon of the GRPR gene in Japanese patients with autism (DSM-IV) and healthy subjects. The two polymorphic sites were at high linkage disequilirium, consistent with a previous study in a North American population. The C450-C661 allele, which was observed in one-third of the chromosomes from the North American subjects, was less frequent (6-7%) in the Japanese subjects, suggesting a large ethnic difference in the frequency of the polymorphism. The allele frequencies and genotype distributions were not significantly different between the patients and controls. However, further studies are required to exclude the GRPR locus as a candidate locus for autism, considering the low frequency of the polymorphism in the Japanese subjects.

Adolescent↗

PubMed2004

Association of the XBP1-116C/G polymorphism with schizophrenia in the Japanese population.

Schizophrenia and bipolar disorder share some clinical features and linkage studies have shown that several loci are common. Recently, the authors found that the -116C-->G substitution in the promotor region of XBP1, a pivotal gene in endoplasmic reticulum (ER) stress response, causes the impairment of ER stress response, and that the -116C/C genotype is a protective factor; in other words the presence of the G allele increases the risk for bipolar disorder. The gene is located on 22q12.1, which is also linked with schizophrenia. The polymorphisms were investigated in 234 schizophrenic patients as compared with controls. Significant difference of genotype distribution was observed, which suggested that the -116C/C genotype is a protective factor for both of the major mental disorders.

Alleles↗

PubMed2003

Serotonin transporter-linked promoter region polymorphism and personality traits in a Japanese population.

Serotonin transporter gene may play a critical role in a regulation of mood and other aspects of mental status. A large number of association studies have investigated a correlation between the polymorphism in the serotonin transporter-linked promoter region (5-HTTLPR) and anxiety-related personality traits. The results, however, have been inconsistent. Heterogeneity of subjects regarding gender, occupation, social-class and other environmental factors, in addition to effects of other genes, might have confounded the results. Here, we studied an association between the 5-HTTLPR polymorphism and personality traits in primarily female (78%) healthy subjects (n=244), who had homogeneous backgrounds regarding ethnicity (Japanese) and occupation. Personality traits of the subjects were assessed with the revised NEO Personality Inventory. No significant association was observed between the polymorphism and neuroticism or other personality traits, in all subjects, all females (n=190) or female nurses (n=159). Thus, our findings provided no evidence for an association between the 5-HTTLPR polymorphism and anxiety-related or other personality traits.

Adult↗

PubMed2002

Human leukocyte antigen-A specificities and its relation with season of birth in Japanese patients with schizophrenia.

Several studies, including one from Japan, have observed an increase of Human Leukocyte Antigen (HLA)-A24 and A26 in schizophrenia, although others failed to observe the increase. No use of systematic diagnostic criteria and a not-adequately reliable typing technique might have affected the results in the previous studies. We investigated HLA-A specificities in Japanese patients with schizophrenia (DSM-IV), recruited from the same area as in the early Japanese study. A DNA-based technique (polymerase chain reaction-microtiter plate hybridization) was employed. No significant difference was observed in frequencies of any HLA-A specificities between patients and controls, including A24 and A26. No significant association was found between the HLA-A and birth-season in patients. Thus, no evidence was obtained for an association between HLA-A and schizophrenia from the Japanese population.

Adult↗

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↗

PubMed2002

Serum cholesterol, uric acid and cholinesterase in victims of the Tokyo subway sarin poisoning: a relation with post-traumatic stress disorder.

Cholesterol and uric acid, which might correlate with steroidogenesis and monoamine functions, may change under emotionally stressful conditions and in mental disturbances. Among anxiety disorders, an increase of serum cholesterol has been observed in panic disorder. However, the issue has not been adequately investigated in other anxiety disorders, including post-traumatic stress disorder (PTSD). The present study investigated serum cholesterols, uric acid and cholinesterase in victims of the Tokyo subway sarin poisoning, 1995, in a series of 5-year follow-ups. Cholinesterase was studied, in relevance with serum lipid changes and symptoms of PTSD, and also in light of a biological effect of sarin. Out of 34 victims, eight developed PTSD and two were currently diagnosed with PTSD using the Clinician-Administered PTSD Scale (CAPS). No significant relationship was observed between PTSD and serum cholesterols or uric acid. Several factors including co-occurrence of other mental disturbances with PTSD, in addition to the limited sample size, might have affected the result. In contrast, serum cholinesterase level was significantly reduced in the victims with the development of PTSD, compared with the matched controls (P<0.02, t-test). This might partly reflect a long-term remnant effect of sarin intoxication, although an effect of the psychological experience could not be totally excluded.

Adult↗