Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Association of neurotrophin-3 gene variant with severe forms of schizophrenia. 773 19

Studies of the trophic activities of brain-derived neurotrophic factor and neurotrophin-3 indicate that both molecules support the survival of a number of different embryonic cell types in culture. We have shown that mRNAs for brain-derived neurotrophic factor and neurotrophin-3 are localized to specific ventral mesencephalic regions containing dopaminergic cell bodies, including the substantia nigra and ventral tegmental area. In the present study, in situ hybridization with 35S-labeled cRNA probes for the neurotrophin mRNAs was combined with neurotoxin lesions or with immunocytochemistry for the catecholamine-synthesizing enzyme tyrosine hydroxylase to determine whether the dopaminergic neurons, themselves, synthesize the neurotrophins in adult rat midbrain. Following unilateral destruction of the midbrain dopamine cells with 6-hydroxydopamine, a substantial, but incomplete, depletion of brain-derived neurotrophic factor and neurotrophin-3 mRNA-containing cells was observed in the ipsilateral substantia nigra pars compacta and ventral tegmental area. In other rats, combined in situ hybridization and tyrosine hydroxylase immunocytochemistry demonstrated that the vast majority of the neurotrophin mRNA-containing neurons in the substantia nigra and ventral tegmental area were tyrosine hydroxylase immunoreactive. Of the total population of tyrosine hydroxylase-positive cells, double-labeled neurons constituted 25-50% in the ventral tegmental area and 10-30% in the substantia nigra pars compacta, with the proportion being greater in medial pars compacta. In addition, tyrosine hydroxylase/neurotrophin mRNA coexistence was observed in neurons in other mesencephalic regions including the retrorubral field, interfascicular nucleus, rostral and central linear nuclei, dorsal raphe nucleus, and supramammillary region. The present results demonstrate brain-derived neurotrophic factor and neurotrophin-3 expression by adult midbrain dopamine neurons and support the suggestion that these neurotrophins influence dopamine neurons via autocrine or paracrine mechanisms. These data raise the additional possibility that inappropriate expression of the neurotrophins by dopaminergic neurons could contribute to the neuropathology of disease states such as Parkinson's disease and schizophrenia.
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PMID:Dopaminergic neurons in rat ventral midbrain express brain-derived neurotrophic factor and neurotrophin-3 mRNAs. 791 99

The recent possible neurodevelopmental etiology of schizophrenia makes the neurotrophin-3 (NT-3) gene an interesting candidate locus. We studied the allelic distributions of dinucleotide repeat polymorphism at the NT-3 gene locus in 70 patients with schizophrenia and in 70 controls. A highly significant difference between the two groups was observed at the allele A3. Even Bonferroni's correction was used, the difference was still significant. Individuals with homozygous or heterozygous for the allele A3 had a 2.4-fold increased risk of schizophrenia. Determination of NT-3 genotype may help to identify those at greater risk of schizophrenia. Furthermore, this finding supports evidence implicating neurodevelopmental deficit in the pathogenesis of this disorder.
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PMID:Neurotrophin-3 gene polymorphism associated with schizophrenia. 808 68

Since abnormalities of brain development play a role in the aetiology of schizophrenia, growth factors, known to play a role in neurodevelopment, such as neurotrophin-3 (NT-3), are therefore candidate genes for this disorder. The A3/147 bp allele of a dinucleotide repeat polymorphism in the promoter region of the NT-3 gene has been reported as occurring more frequently in a sample of Japanese schizophrenics compared to controls. We have determined the frequency of alleles of this polymorphism in 175 Caucasian schizophrenic patients and 147 control subjects. The patient and control samples showed no significant deviation from Hardy-Weinberg equilibrium and, in a test of allalleles, the patients and controls did not differ significantly in allele frequencies. However, the male schizophrenics were more likely than male controls to have the A3/147 bp allele (P = 0.029).
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PMID:An association study of a neurotrophin-3 (NT-3) gene polymorphism with schizophrenia. 883 68

A case-control association study was conducted among patients with schizophrenia (DSM-III-R, n = 141) and unaffected controls (n = 177) of Caucasain and African-American ethnicity. No significant differences in the distribution of a dinucleotide repeat polymorphism in the neurotrophin-3 (NT-3) gene were noted between the two groups. This study does not support an association between schizophrenia and the NT-3 gene locus in a United States cohort.
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PMID:Lack of association of schizophrenia with the neurotrophin-3 gene locus. 883 75

This study aimed to replicate positive associations between polymorphisms of the neurotrophin-3 gene and schizophrenia. The reported associations, which were the results of searching for mutations in the locus in schizophrenics under the hypothesis of neurodevelopmental etiology of schizophrenia, are that the states carrying the (CA)23 allele of the CA repeat in the first intron have a 2.56-fold increased risk of schizophrenia and those carrying the allele Glu-63 instead of Gly-63 have a 2.6-fold increased risk of schizophrenia with onset before 25 years and with duration of the illness of more than 10 years. We analyzed these polymorphisms in 80 schizophrenics with onset before 25 years of age and with duration of illness of more than 10 years and 80 age-matched psychosis-free controls. With our sample size, there was a 90% chance of detecting odds ratios observed in initial positive reports. We found similar allele and genotype frequencies of both polymorphisms between the schizophrenic and control groups. We failed to support associations between the polymorphisms of the neurotrophin-3 gene analyzed and schizophrenia.
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PMID:Failure to find associations of the CA repeat polymorphism in the first intron and the Gly-63/Glu-63 polymorphism of the neurotrophin-3 gene with schizophrenia. 892 52

It has been suggested on the basis of neuropathological and epidemiological evidence that schizophrenia is, at least in part, a neurodevelopmental illness. Some patients show abnormalities in cell position in the medial temporal lobes of their brains. Neurotrophin-3 is one of many proteins essential for the proper growth and development of the nervous system. Therefore the finding of a polymorphism near the promoter region of the gene, alleles of which were associated with the disease, prompted us to attempt replication. In a linkage and association analysis of the same polymorphism using familial schizophrenics and population controls we found no evidence to support the finding. We conclude that mutations or polymorphisms at this gene are unlikely to be involved in the genetic aetiology of schizophrenia.
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PMID:Neurotrophin-3 gene polymorphisms and schizophrenia: no evidence for linkage or association. 914 22

Studies of brain anatomy and premorbid functioning indicate that schizophrenia may be of neurodevelopmental origin. In the neurotrophic factor neurotrophin-3 (NT-3) gene, the A3/147-bp allele in a dinucleotide repeat polymorphism located in the promoter region was found to be associated with schizophrenia in a Japanese study. Another NT-3 polymorphism (Glu63Gly) indicated an association with schizophrenic patients with a putative neurodevelopmental form of the disease. We examined Swedish schizophrenic patients (n = 109) and control subjects (n = 78) for the same two NT-3 polymorphisms, as well as a third silent exonic polymorphism (at Pro55). No significant difference was found between the two groups. However, in a meta-analysis including the present and previous studies of Caucasian subjects, the A3/147-bp allele frequency was found to be significantly higher in the schizophrenic patients. In the present study, carriers of the A3/147 bp allele tended to have an earlier age of onset and to display more extrapyramidal symptoms. In the silent exonic polymorphism (at Pro55), female schizophrenic patients had higher adenine and lower guanine allele frequencies than control female subjects. Together with previous studies, the results provide some support for an association between the NT-3 gene and certain forms of schizophrenia. This warrants further investigation of NT-3 and other neurotrophic factors with additional polymorphisms and larger patient samples.
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PMID:Schizophrenia and neurotrophin-3 alleles. 919 6

Neurotrophin-3 (NT-3) may have a potential role in the pathogenesis of schizophrenia, given evidence of abnormal neurodevelopment in schizophrenia, as well as a potential association of an NT-3 gene polymorphism with schizophrenia. Cerebrospinal fluid NT-3 protein was assayed using an enzyme-linked immunosorbent assay in five patients with schizophrenia and 49 patients with medical illness. None of the patients with schizophrenia had detectable levels of NT-3 (above 4.7 pg/ml). Eleven samples from 10 different patients with medical or neurological illness had detectable levels of NT-3, associated with surgery for hydrocephalus or central nervous system infection.
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PMID:Neurotrophin-3 levels in the cerebrospinal fluid of patients with schizophrenia or medical illness. 946 44

There is increasing evidence that a neurodevelopmental process is accountable for at least a proportion of schizophrenic cases. Brain-derived neurotrophic factor (BDNF), a member of a group of proteins that includes neurotrophin-3/4/5 and nerve growth factor (NGF), is an attractive candidate gene. We have performed a case control association study using the BDNF dinucleotide repeat polymorphism in a sample of familial schizophrenic individuals and in healthy, ethnically matched control subjects. We also performed a linkage analysis on 265 multiplex families using the same marker. We found no differences in allele frequencies between the patient and control groups nor any evidence for transmission disequilibrium or linkage with the multiply affected families. We conclude that DNA variation at or near the BDNF gene is unlikely to contribute to the genetic predisposition to schizophrenia.
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PMID:No linkage or linkage disequilibrium between brain-derived neurotrophic factor (BDNF) dinucleotide repeat polymorphism and schizophrenia in Irish families. 985 28


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