A case of bipolar disorder with balanced chromosomal translocation.
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Aged↗
Biomedical subjects
S Nanko
Publications and source records attributed to S Nanko.
No evidence of linkage or association between tyrosine hydroxylase gene and affective disorder.
Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the synthesis of dopamine and norepinephrine, and therefore is of significant interest as a candidate gene in studies of affective disorders. We have carried out the linkage study between the susceptibility gene for affective disorder and tetranucleotide polymorphism of TH gene in five Japanese pedigrees. In addition to the linkage approach, we have undertaken an allelic association study using 74 patients with affective disorder and 78 controls with polymorphisms at the TH gene and the nearby dopamine D4 receptor gene. No evidence for linkage or associations were found. These results indicate that TH gene is less likely to contribute to the genetic component of affective disorders.
Adolescent↗
Linkage studies on chromosome 22 in familial schizophrenia.
As part of a systematic search for a major genetic locus for schizophrenia we have examined chromosome 22 using 14 highly polymorphic markers in 23 disease pedigrees. The markers were distributed at an average distance of 6.6 cM, covering 70-80% of the chromosome. We analyzed the data by the lod score method using five plausible genetic models ranging from dominant to recessive, after testing the power of our sample under the same genetic parameters. The most positive lod score found was 1.51 under a recessive model for the marker D22S278, which is insufficient to conclude linkage. However, an excess of shared alleles in affected siblings (P < .01) was found for both D22S278 and D22S283. For D22S278, the A statistic was equal to the lod score (1.51) and therefore did not provide additional evidence for linkage allowing for heterogeneity, but the Liang statistic was more significant (P = .002). Our results suggest the possibility that the region around D22S278 and D22S283 contains a gene which contributes to the aetiology of schizophrenia.
Alleles↗
Association of neurotrophin-3 gene variant with severe forms of schizophrenia.
The recent possible neurodevelopmental etiology of schizophrenia makes neurotrophin-3 (NT-3) gene an interesting candidate locus for molecular study of schizophrenia. We searched DNA variants through the coding region and the AP-1 binding site of the NT-3 gene, and found three variants. One is a missense mutation, Gly-63-->Glu-63 (GGG-->GAG), and the others are silent mutations. None of them have been associated with schizophrenia. However, a significant difference was found in the distribution of the variant, Gly-63-->Glu-63, between 61 patients and 101 controls, when the patients were restricted to severe cases based on the neurodevelopmental perspective. Individuals homozygous or heterozygous for the allele Glu-63 had a 2.595-fold increased risk of severe forms of schizophrenia.
Adolescent↗
Early parental loss and depressive disorder in Japan.
The aim of this study is to determine in a Japanese sample whether or not the permanent loss of a parent by death or separation in childhood is aetiologically associated with unipolar major depressive disorder (according to RDC). We compared the incidence of parental loss before 17 years of age by death or separation between 122 depressed inpatients and 94 non- and never-depressed medical controls. Early maternal death was found to be significantly more common in the depressives than in the controls. Separation from either parent also showed a trend towards an increased incidence in the depressive group. No significant difference in the incidence of early paternal death was found.
Adolescent↗
Genetic association of the very low density lipoprotein (VLDL) receptor gene with sporadic Alzheimer's disease.
A specific isoform of apolipoprotein E has been associated with the accelerated rate of disease expression of sporadic Alzheimer's disease (AD) and late-onset familial AD (FAD). An earlier age at onset has also been demonstrated in familial AD patients with mutations in the amyloid precursor protein (APP) gene (APP717 and APP670/671)13 carrying the APOE epsilon-4 allele compared to those who do not, but not in familial AD patients with APP692 or 693 mutations, or in chromosome 14-linked familial AD patients. Hypothesizing that receptors for apoE-containing lipoproteins act as a potential risk factor for AD, we performed an association study using a polymorphic triplet (CGG) repeat in the gene for the VLDL receptor (VLDL-R), a receptor for apoE-containing lipoproteins. The frequency of the 5-repeat allele was significantly higher in all of the Japanese sporadic AD patients (P < 0.02) than in the Japanese controls. Moreover, the odds ratio was significantly increased in the AD patients homozygous for the 5-repeat allele (OR = 2.1, 95% CI = [1.1-4.2]). Multiple logistic regression analysis reveals that the relative risk conferred by the presence of two copies of the 5-repeat allele and at least one copy of the APOE epsilon-4 allele is 8.7 (95% CI = [2.9-25.8]). Our results suggest that the VLDL-R gene is a susceptibility gene for AD.
Alleles↗
Schizophrenia following in utero exposure to the 1957 influenza epidemics in Japan.
OBJECTIVE: Studies in Finland, England, and Denmark have reported that individuals exposed to the 1957 A2 influenza pandemic during their second trimester in utero are at greater risk for later schizophrenia. However, other studies in England, the United States, and Holland reported no such association. The authors' goal was to shed light on these conflicts. METHOD: They compared the number of individuals who later developed schizophrenia who were born in the 5 months after the peak prevalence of three distinct 1957 influenza epidemics in Japan with the mean number of individuals who later developed schizophrenia who were born in the corresponding months of the 4 years surrounding the epidemics. RESULTS: A significantly greater number of females but not males who later developed schizophrenia were born during the risk exposure months than in the non-risk-exposure months. CONCLUSIONS: These findings, although weak, lend support to the claim that in utero exposure to influenza epidemics is a risk factor for adult schizophrenia.
Adult↗
Possible association between monoamine oxidase A gene and bipolar affective disorder.
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Alleles↗
No allelic association between Parkinson's disease and dopamine D2, D3, and D4 receptor gene polymorphisms.
Parkinson's disease is thought to be caused by a combination of unknown environmental, genetic, and degenerative factors. Evidence from necropsy brain samples and pharmacokinetics suggests involvement of dopamine receptors in the pathogenesis or pathophysiology of Parkinson's disease. Genetic association studies between Parkinson's disease and dopamine D2, D3 and D4 receptor gene polymorphisms were conducted. The polymorphism was examined in 71 patients with Parkinson's disease and 90 controls. There were no significant differences between two groups in allele frequencies at the D2, D3, and D4 dopamine receptor loci. Our findings do not support the hypothesis that susceptibility to Parkinson's disease is associated with the dopamine receptor polymorphisms examined.
Adult↗
No evidence of linkage or allelic association of schizophrenia with DNA markers at pericentric region of chromosome 9.
Based on our previous study suggesting the pericentric region of chromosome 9 as of potential importance in schizophrenia, we have carried out a linkage study between the schizophrenia phenotype and the dinucleotide repeat polymorphisms D9S55, D9S15, and D9S202 in three pedigrees multiply affected with schizophrenia. In addition, we have conducted allelic association studies using 60 patients with schizophrenia and 60 controls with polymorphisms at D9S55 and D9S15 markers. No evidence for linkage or association was found. The results indicate that susceptibility genes for schizophrenia are less likely to be located at the pericentric region of chromosome 9, assuming genetic homogeneity of the pedigrees.
Alleles↗
Further evidence of no linkage between schizophrenia and the dopamine D3 receptor gene locus.
The dopamine hypothesis of schizophrenia proposed that dopaminergic pathways are involved in the etiology of the disease. In particular, interest among psychiatrists has focused on the D2 receptor because of its affinity to antipsychotic drugs. Recently a new dopamine receptor gene has been cloned, and named the dopamine D3 receptor. The D3 receptor is a potential site for antipsychotic drug action and may be involved in the pathophysiology of schizophrenia. We have carried out a linkage study between the susceptibility gene for schizophrenia and polymorphism of the dopamine D3 receptor gene in two Japanese pedigrees. The LOD scores were negative for all genetic models and for all affective status at a recombination fraction theta = 0. Linkage of DRD3 has been excluded for the model 1 (dominant model) and the model 3 (recessive model). The LOD score was -3.43 at theta = 0 for model 1 (dominant model) and broad definition of affected status. These results were consistent with previous studies.
DNA↗
Mismatch PCR RFLP detection of DRD2 Ser311Cys polymorphism and schizophrenia.
We tested 100 schizophrenics and 100 controls to find association at the Serine311 Cysteine polymorphism of dopamine D2 receptor in Japanese population. There were no significant differences between the two groups. One homozygote for Cys311 was confirmed in the controls by mismatch-polymerase chain reaction and restriction fragment length of polymorphism (PCR-RFLP) analysis. None with Cys was detected among 61 individuals of nine multiply affected families with schizophrenia. Our data thus provide strong evidence against an etiological association between schizophrenia and the Ser311Cys variant. The polymerase chain reaction amplification of specific alleles (PASA) analysis was compared with the mismatch PCR-RFLP typing, revealing that the latter is more reliable than the former.
Alleles↗
Association of apolipoprotein E4 with sporadic Alzheimer's disease is more pronounced in early onset type.
Apolipoprotein E genotypes in 88 unrelated Japanese patients with NINCDS-ADRDA sporadic Alzheimer's disease (AD) were examined and compared with those of 93 healthy controls. Frequency of epsilon 4 allele was increased in patients with AD (31%) compared with controls (10%), as was reported previously. Individuals homozygous or heterozygous for the allele epsilon 4 had a 5.9-fold increased risk of AD. This tendency was more pronounced in early onset sporadic (= non-familial) type than late onset type. The relative risk was also greater for early onset type (RR = 11.7; 95% CI, 4.9-28.3) than late onset type (RR = 4.3; 95% CI, 2.1-8.8). Moreover, patients with homozygote for the allele epsilon 4 had a 14.7-fold increased risk of early onset sporadic AD (P < 0.005, chi 2 = 9.0, df = 1, 95% CI, 2.5-85.1). Our findings indicated that association of apolipoprotein epsilon 4 with sporadic Alzheimer's disease is more pronounced in early onset type than in late onset type.
Age of Onset↗
DRD2 Ser311/Cys311 polymorphism in schizophrenia.
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Cysteine↗
Failure to find linkage between a functional polymorphism in the dopamine D4 receptor gene and schizophrenia.
We report the results of a linkage study in 24 families multiply affected with schizophrenia using a polymorphic DNA sequence encoding the third cytoplasmic loop of the dopamine D4 receptor. Two-point LOD score analyses with a range of single gene models ranging from near dominant to near recessive revealed no evidence for linkage. In addition, we examined the data by non-parametric sib-pair analysis and found no excess sharing of alleles between affected sib-pairs. We therefore conclude that mutations within the dopamine D4 receptor gene do not have a major aetiological role in schizophrenia in our collection of pedigrees.
Alleles↗
Changes of immunological functions after acute exacerbation in schizophrenia.
We investigated the changes of immunological functions in 14 schizophrenic patients (DSM-III-R; six men and eight women) who were hospitalized due to acute exacerbation of schizophrenia. The following immunological functions were studied on admission, 4 and 8 weeks after admission: serum immunoglobulins (Ig)G, A, and M; serum complement CH50; lymphocyte responses to mitogens (phytohemagglutinin, concanavalin A, and pokeweed mitogen); lymphocyte subpopulations (CD3%, 4%, 8%, 16%, 20%, 25%, and 56%); and natural killer cell (NK) activity. Psychological status of the patients, which was assessed by using Brief Psychiatric Rating Scale, improved gradually after admission. Changes in immune functions were analyzed using one-way analysis of variance and a randomized block analysis of variance with multiple comparison. NK activity on admission was significantly lower than those at 4 and 8 weeks after admission (p < .03). Serum IgG levels on admission and at 4 weeks after admission were significantly decreased as compared with those at 8 weeks after admission (p < .05); they were also lower than those in controls (p < .05). CD56% on admission and CD25% 4 weeks after admission were significantly increased as compared with controls (p < .05). These results indicate that several immunological functions might change related to time course after acute exacerbation. It is suggested that clinical conditions be carefully taken into consideration to evaluate immunological studies in schizophrenia.
Acute Disease↗
Linkage studies between affective disorder and dopamine D2, D3, and D4 receptor gene loci in four Japanese pedigrees.
Dopamine antagonists are effective in the treatment of episodes of acute mania. Conversely, drugs which increase dopamine activity can induce a switch to mania. Therefore, disturbances in dopamine transmission and dopamine receptors might be implicated in the pathophysiology of bipolar affective disorder. We have carried out linkage studies between the susceptibility gene for effective disorder and polymorphisms of dopamine DRD2, DRD3, and DRD4 receptor genes in four Japanese pedigrees. Linkages of both DRD2 and DRD3 have been excluded, at least for dominant and intermediate models. The result for DRD2 was consistent with previous studies. For DRD3 this is the first exclusion of affective disorder from this locus in the 3q13.3 where DRD3 has been localized. On the other hand, our data could not exclude linkage of DRD4.
Adolescent↗
HLA-DR types in Japanese schizophrenics: analysis by group-specific PCR amplification.
An association of HLA-DR8 and DR1 with DSM-III schizophrenia has been reported in Japan (Miyanaga et al. (1984) Biol. Psychiatr. 19, 121-129). To further investigate this preliminary finding, we compared HLA-DR types in 44 unrelated Japanese schizophrenics (DSM-III-R) with those in 51 unrelated, healthy Japanese volunteers. Group-specific PCR amplification was used in the determination of HLA-DR in the patients. No significant difference was observed in the frequency of any DR types between patients and controls, after statistical correction for multiple testing. However, the frequency of DR1 in our patients (23%) and controls (10%) was almost the same as those in the previous report (22% vs. 10%), which means that there is a suggestive trend which could become significant if numbers were larger. It is argued that an exact determination of HLA-DR by DNA typing is important in current HLA studies of schizophrenia.
Adult↗