Brain-derived neurotrophic factor gene and schizophrenia in Japanese subjects.
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Adult↗
Biomedical subjects
S Nanko
Publications and source records attributed to S Nanko.
Schizophrenia and the ciliary neurotrophic factor (CNTF) gene: no evidence for association.
The ciliary neurotrophic factor (CNTF) gene is considered a candidate gene for schizophrenia, in view of the neurodevelopmental hypothesis of the disorder. Recently, controversial results regarding an association between psychiatric disorders; mainly schizophrenia, and a null mutation of the CNTF gene were reported. We investigated this mutation in 138 Japanese patients with schizophrenia and 140 healthy control subjects. No significant difference was observed in allele frequencies or genotype distribution between the patients and control subjects. Our results did not provide evidence for the involvement of the null mutation of the CNTF gene in the development of schizophrenia.
Adult↗
Genes for interleukin-2 receptor beta chain, interleukin-1 beta, and schizophrenia: no evidence for the association or linkage.
We studied a CA repeat polymorphism of the interleukin-2 receptor beta chain (IL-2RB) gene and a C/-514/T variation of the interleukin-1 beta (IL-1B) gene in Japanese schizophrenia patients. Both a case-control association study (54 patients and 54 controls) and a linkage study using six multiplex families (the number of the affected > or =4 in each family) were employed. No evidence for the association or the linkage was obtained either for the IL-2RB or IL-1B gene.
Alleles↗
High and low activity alleles of catechol-O-methyltransferase gene: ethnic difference and possible association with Parkinson's disease.
Catechol-O-methyltransferase (COMT) is an enzyme that inactivates catecholamines such as adrenaline, noradrenaline, dopamine, and levodopa. Recently an amino acid change (Val-108-Met) of the COMT protein was found to determine high and low activity alleles of the COMT gene. We genotyped 109 Japanese patients with Parkinson's disease (PD) and 153 controls by using polymerase chain reaction (PCR) amplification and digestion by the restriction enzyme NlaIII. The frequency of low activity allele in the controls was 0.29, which was significantly different from that reported in Caucasians (0.50). When comparison was made between patients with PD and controls, homozygosity for the low activity allele was significantly more common among the patients than among the controls (P = 0.017; odds ratio, 2.8, 95% CI 1.2-6.5), suggesting that homozygosity for the low activity allele may increase susceptibility to PD.
Adult↗
Low serum cholesterol in suicide attempters.
Previous studies have shown an association between low serum cholesterol concentration and suicide; however, conflicting results have also been reported. To examine this potential association, cholesterol levels in 99 patients admitted to an emergency ward following an attempted suicide were compared with those in 74 nonsuicidal psychiatric inpatients, and those in 39 psychiatrically normal individuals with accidental injuries. Cholesterol concentrations in suicide attempters were found to be significantly lower compared with both psychiatric and normal controls, when sex, age, psychiatric diagnosis, and physical conditions (serum total protein and red blood cell count) were adjusted for. This significant relationship was observed in mood disorders and personality or neurotic disorders, but not in schizophrenia spectrum disorders. These results support the previous claim that lower cholesterol level is associated with an increased risk of suicidal behavior.
Adult↗
Catechol-O-methyltransferase polymorphisms and schizophrenia: a transmission disequilibrium study in multiply affected families.
Catechol-O-methyltransferase (COMT) metabolizes catecholamines such as dopamines, noradrenaline and adrenaline. It exists as common high and low activity alleles in the population (determined by a valine 158 methionine polymorphisms), and high red blood cell activity of COMT has previously been associated with schizophrenia. To examine the relationship between COMT and schizophrenia genetically, the transmission disequilibrium test was performed on 22 multiply affected Caucasian and Japanese families genotyped for val158met and a second, silent, polymorphism (C256G), using PCR based assays. The high activity val158 allele was transmitted from parents to the affected individuals more frequently than the low activity met158 allele, although this was not statistically significant. Combining this data with a previous study using Chinese family trios with schizophrenia (Li et al., 1996) gave a highly significant result (p = 0.0015). The G256 allele was also transmitted preferentially to the affected offspring, and this was statistically significant when schizophrenia, schizoaffective disorder and unspecified functional psychosis were included in the definition of the affected phenotype (p = 0.03). Overall, these findings may indicate an effect of COMT alleles on susceptibility to schizophrenia, or reflect linkage disequilibrium with a different causative polymorphism in the vicinity. Other reported associations of COMT with obsessive compulsive and rapid cycling bipolar disorder indicate that the COMT gene may have complex and pleiotropic effects on susceptibility and symptomatology of neuropsychiatric disorders.
Amino Acid Substitution↗
Season of birth of schizophrenics in a recent Japanese sample.
An excess of schizophrenic births in winter or early spring is a well replicated finding in studies on Western populations. However, there are few studies on Asian populations, and their results are not consistent. We examined the seasonality of schizophrenic births in Japanese subjects (n = 1024) born between 1955 and 1960. Our results showed a significant inverse relationship between temperature and number of schizophrenic births, which is in line with the findings in Western populations. In our data, observed reduction of schizophrenic births in summer was more marked than excess births in winter. We suggest the possibility that birth in summer may have some advantage in brain growth early in life, which results in reducing the risk of developing schizophrenia.
Adult↗
A linkage study of schizophrenia with DNA markers from chromosome 8p21-p22 in 25 multiplex families.
Two recent genome-wide searches for linkage (Lasseter et al., 1994; Moises et al., 1995) suggested that a susceptibility gene for schizophrenia might be located at chromosome 8p21-p22. We attempted to replicate these findings by performing a linkage study of schizophrenia with four DNA markers from this region using 25 multiply affected families. Neither the lod score method nor non-prametric extended sib-pair analysis yielded any evidence for linkage, even under the assumption of locus heterogeneity. We conclude that there is unlikely to be a major gene in the 8p21-p22 region which confers susceptibility to schizophrenia in our set of families. However we cannot exclude the possibility of a major gene present in other families, or of a susceptibility gene with a moderate but widespread effect which we cannot detect.
Autoradiography↗
Manic-depressive illness and tyrosine hydroxylase gene.
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Alleles↗
5HT 2a receptor T102C polymorphism and schizophrenia.
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Genotype↗
Serotonin transporter gene polymorphism and affective disorder.
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Alleles↗
A combined analysis of D22S278 marker alleles in affected sib-pairs: support for a susceptibility locus for schizophrenia at chromosome 22q12. Schizophrenia Collaborative Linkage Group (Chromosome 22).
Several groups have reported weak evidence for linkage between schizophrenia and genetic markers located on chromosome 22q using the lod score method of analysis. However these findings involved different genetic markers and methods of analysis, and so were not directly comparable. To resolve this issue we have performed a combined analysis of genotypic data from the marker D22S278 in multiply affected schizophrenic families derived from 11 independent research groups worldwide. This marker was chosen because it showed maximum evidence for linkage in three independent datasets (Vallada et al., Am J Med Genet 60:139-146, 1995; Polymeropoulos et al., Neuropsychiatr Genet 54:93-99, 1994; Lasseter et al., Am J Med Genet, 60:172-173, 1995. Using the affected sib-pair method as implemented by the program ESPA, the combined dataset showed 252 alleles shared compared with 188 alleles not share (chi-square 9.31, 1df, P = 0.001) where parental genotype data was completely known. When sib-pairs for whom parental data was assigned according to probability were included the number of alleles shared was 514.1 compared with 437.8 not shared (chi-square 6.12, 1df, P = 0.006). Similar results were obtained when a likelihood ratio method for sib-pair analysis was used. These results indicate that may be a susceptibility locus for schizophrenia at 22q12.
Alleles↗
No association between Parkinson's disease and monoamine oxidase A and B gene polymorphisms.
Parkinson's disease (PD) is thought to be caused by a combination of unknown environmental, genetic and degenerative factors. Among these factors, monoamine oxidase has been considered as a possible factor in the pathophysiology of Parkinson's disease. We have carried out allelic association studies of PD with monoamine oxidase type A (MAOA) and monoamine oxidase type B (MAOB) gene loci using dinucleotide repeat polymorphisms. Distributions of all alleles at MAOA and MAOB gene loci were almost similar in patients and controls. Contrary to previous reports, our findings could not support the hypothesis that susceptibility to PD is associated with MAOA or MAOB polymorphism.
Adult↗
Small head circumference at birth in schizophrenia.
The growing evidence for neurodevelopmental basis to schizophrenia has focused attention on the prenatal development of individuals who later develop the illness. Several previous studies have shown reduced birth weight (BW) in schizophrenics and one recently reported smaller birth head circumference (BHC). The current study compared 67 DSM-III-R schizophrenics and a general population group of 1640, using information obtained from contemporaneous birth records. When gestational age and gender were controlled for, no significant difference was found in BW between the schizophrenics and the comparison population. However, the preschizophrenics showed significantly smaller BHC for gestational age, suggestive of slower fetal brain growth.
Adult↗
Perinatal complications and schizophrenia. Data from the Maternal and Child Health Handbook in Japan.
A number of studies have shown that schizophrenics have increased obstetric complications compared with controls, but conflicting negative results have also been reported. Similarly, some studies found that obstetric complications were more frequently observed among male or nonfamilial schizophrenics than their female or familial schizophrenic counterparts, but others reported negative or inverse results. Since 1948 in Japan, every pregnant woman has been assigned a Maternal and Child Health Handbook in which obstetricians have been obliged to fill in obstetric data. In the current study, perinatal complications assessed using the scale of Parnas et al. (1982), based on information from the maternal and child health handbook were compared between DSM-III-R-diagnosed schizophrenics (N = 59), their healthy siblings (N = 31), and controls (N = 108). We found that female schizophrenics had experienced significantly more perinatal complications than siblings and controls. We could not detect any significant association between perinatal complications and family history.
Comorbidity↗
Linkage analysis of the fragile X gene FMR-1 and schizophrenia: no evidence for linkage but report of a family with schizophrenia and an unstable triplet repeat.
We have examined 23 families multiply affected with schizophrenia for linkage to the FMR-1 gene on the X chromosome. Alleles at the FMR-1 CGG triplet repeat were analysed by the polymerase chain reaction, and methylation status at the FMR-1 locus in individuals with evidence of expanded or unstable repeats was analysed by Southern hybridization. Two-point LOD score analyses with a range of X-linked single gene models and a non-parametric affected sib-pair method revealed no evidence for linkage. In one family, however, a fragile X premutation was found, and one individual with schizophrenia and developmental delay was a mosaic for the full and premutation. We conclude that although mutations within the FMR-1 gene do not have a major aetiological role in schizophrenia in our collection of pedigrees, it is possible that FMR-1 mutations can modify the clinical phenotype of schizophrenia.
Adolescent↗
No association between c-fos gene polymorphisms and sporadic Alzheimer's disease.
Although ApoE epsilon 4 is a major risk factor for sporadic Alzheimer's disease (AD), 20-30% of sporadic AD patients do not have this allele. This indicates that other risk factors are involved in the pathogenesis of sporadic AD. Studies of the genetic association between AD and polymorphisms in the c-fos gene, a candidate gene for AD, were conducted. The polymorphisms of DsaI in exon 2 and Sau3 AI in intron 2 were examined in 89 patients diagnosed as sporadic cases of probable AD clinically and radiologically according to the NINCDS-ADRDA criteria. This was also undertaken in 96 controls. There was no significant difference between the groups in allele frequencies or genotype counts. Although c-fos gene as a locus conferring susceptibility to sporadic AD cannot be ruled out, these data could not support the hypothesis that a c-fos allele should be another risk factor for sporadic AD.
Aged↗
Schizophrenia and the androgen receptor gene: report of a sibship showing co-segregation with Reifenstein syndrome but no evidence for linkage in 23 multiply affected families.
Crow et al. [1993: Am J Med Genet (Neuropsychiatr Genet) 48:159-160] have reported excess sharing of alleles by male sibling pairs with schizophrenia, at a triplet repeat marker within the androgen receptor gene, indicating that mutations at or near this gene may be a risk factor for males. In this report, we describe a pair of male siblings concordant for both schizophrenia and Reifenstein syndrome, which is caused by a mutation in this gene. This provides support for the hypothesis that the androgen receptor may contribute to liability to develop schizophrenia. Because of this, we have examined a collection of 23 pedigrees multiply affected by schizophrenia for linkage to the androgen receptor. We have found no evidence for linkage by both the LOD score and affected sibling-pair methods, under a range of genetic models with a broad and narrow definition of phenotype, and when families with male-to-male transmission are excluded. However, because of the small number of informative male-male pairs in our sample, we cannot confirm or refute the excess allele sharing for males reported by Crow.
Adolescent↗