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)

Using a systematically ascertained sample of 57 families, each having 2 or more members with a consensus diagnosis of schizophrenia (DSM-III-R criteria), we have carried out linkage studies of 520 loci, covering approximately 70% of the genome for susceptibility loci for schizophrenia. A two-stage strategy based on lod score thresholds from simulation studies of our sample identified regions for further exploration. In each region, a dense map of highly informative dinucleotide repeat polymorphisms (heterozygosity greater than .70) was analyzed using dominant, recessive, and "affected only" models and nonparametric sib pair identity-by-descent methods. For one region, 8p22-p21, affected sib-pair analyses gave a P value = .0001, corresponding to a lod score approximately equal to 3.00. For 8p22-p21, the maximum two-point lod score occurred using the "affected only" recessive model (ZMAX = 2.35; theta M = theta F); allowing for a constant sex difference in recombination fractions found in reference pedigrees, ZMAX = 2.78 (theta M/theta F = 3). For a second region, 3p26-p24, the maximum two-point lod score was 2.34 ("affected only" dominant model), and the affected sib-pair P value was .01. These two regions are worthy of further exploration as potential sites of susceptibility genes for schizophrenia.
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PMID:Schizophrenia: a genome scan targets chromosomes 3p and 8p as potential sites of susceptibility genes. 757 81

Borna disease virus (BDV) infection has been suspected to be a possible etiological factor in human psychiatric disorders and recently in chronic fatigue syndrome. Evidence of the correlation of BDV infection with these disorders remained unclear. Kagoshima is known to be one of the major areas in which human T-cell leukemia virus type 1 (HTLV-1) is endemic; this is the first isolated human retrovirus that causes adult T-cell leukemia with neurological symptoms. The present study aimed to clarify whether BDV and HTLV-1 infections are associated with psychiatric disorders among Japanese patients. Subjects were 346 patients with psychiatric disorders (schizophrenia, 179; mood disorder, 123; and others, 44) and 70 healthy controls. Anti-BDV antibodies from plasma samples were screened by the indirect immunofluorescence (IF) method using BDV-infected MDCK cells. Results revealed that only three samples were found to be weakly positive for BDV in the IF assay and seronegative by Western blot (immunoblot) assay. Furthermore, BDV-p24 related RNA in peripheral blood mononuclear cells from 106 of 346 psychiatric patients and 12 or 70 healthy controls by p24-reverse transcription PCR was examined. Two mood disorder patients were positive for BDV-p24 RNA but seronegative. To detect anti-HTLV-1 antibodies the plasma samples were screened by the particle agglutination method and no significant difference in seropositivity for anti-HTLV-1 antibody was found between the patients and healthy controls. These results also suggested that there is a lack of association between BDV and HTLV-1 infections with psychiatric disorders among Japanese patients.
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PMID:Lack of association of Borna disease virus and human T-cell leukemia virus type 1 infections with psychiatric disorders among Japanese patients. 906 54

Schizophrenia is a serious and often debilitating neuropsychiatric disease of worldwide importance. Current therapy relies on the use of typical antipsychotic medications, which specifically inhibit binding of ligand at the D2 dopamine receptor, and atypical medications which display little activity for this receptor interaction. While atypical antipsychotic agents have been shown to variably inhibit other neuroreceptor-ligand interactions, the exact mechanisms for the therapeutic efficacy of these medications have not been completely defined. Clozapine, an atypical antipsychotic, and nine of its metabolites were studied in vitro for possible antiviral activity against a model of a human neurotropic virus, human immunodeficiency virus type 1 (HIV-1). In an assay for inhibition of virus-induced cytopathic effect (CPE) two metabolites demonstrated antiviral activity (ID50 = 37-85 micrograms/ml) (119-289 microM), while other atypical or novel antipsychotics as well as typical medications had no effect. Based on an ELISA, four chemically similar metabolites inhibited the production of p24, the major internal antigen of HIV (ID50 = 11.6-15.7 micrograms/ml) (38-51 microM). These data suggest that the therapeutic efficacy of some antipsychotics may be due in part to an ability to inhibit viral replication. Antiviral agents may prove to be effective adjuncts in the treatment of schizophrenia.
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PMID:Metabolites of the antipsychotic agent clozapine inhibit the replication of human immunodeficiency virus type 1. 917 28

Loci conferring susceptibility to schizophrenia, coeliac disease, and orofacial clefting have been assigned to the 6p23-p25 region of human chromosome 6. To facilitate the identification of candidate genes we have sublocalized and ordered 39 ESTs assigned to this interval by radiation hybrid mapping. This was achieved by generating PAC contigs containing the ESTs, genetic markers, and random STSs. For full integration into previously published data a single YAC contig spanning 6p23-p25 was used to unambiguously order the PAC contigs and ESTs along the chromosome. The majority of the ESTs (31/39) were positioned in the 6p23-p24 interval at the proximal half of the map, and of these 8 are located within a single PAC clone. The order of known genes in this region is cen-CD83-ZNF40-EDN1-(GCNT2, CAPZB)-TFAP2-BMP6-DSP-tel.
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PMID:Fine mapping of 39 ESTs on human chromosome 6p23-p25. 941 21

The relationship between Borna disease virus (BDV) infection and positive and negative syndromes in schizophrenia was investigated. By nested RT-PCR and Western blotting, BDV-specific RNA and anti-BDV antibodies were examined in blood from 67 schizophrenic patients (DSM-III-R) in Japan, and the psychometric properties of the Positive and Negative Syndrome Scale (PANSS) were analyzed. There were significant (p < 0.05) differences in the composite index denoting the positive minus negative difference indicating a dominant contribution by negative items, and the proportion of negative type (positive minus negative value below zero) patients, between patients positive and negative for anti-BDV p24 antibodies. It is possible that BDV infection with induction of BDV p24 antibodies may be associated with negative syndromes in schizophrenic patients.
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PMID:Positive and negative syndromes, and Borna disease virus infection in schizophrenia. 956 66

Borna disease virus (BDV) p24 RNA was detected in the peripheral blood mononuclear cells (PBMCs) of psychiatric patients and blood donors by nested reverse transcriptase PCR (RT-PCR). The prevalences of BDV p24 RNA in patients with mood disorders (4%) and schizophrenia (4%) were not significantly different from that in blood donors (2%). This finding was inconsistent with previous reports that showed either a high prevalence or absence of BDV p24 RNA in patients with psychiatric disorders. The differences in BDV p24 RNA prevalence in these studies may be due to differences in the criteria for positivity, the number of PBMCs used for RNA extraction, or the amount of RNA tested for nested RT-PCR or to laboratory contamination. Sequence analysis of BDV p24 RNA from the PBMCs of patients and blood donors showed a high nucleotide sequence conservation but definite nucleotide mutations compared with horse BDV p24 RNA sequences. In comparison with human BDV p24 RNA sequences previously reported from Japan and Germany, there were several positions with silent nucleotide mutations among these clones.
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PMID:Detection and sequence analysis of borna disease virus p24 RNA from peripheral blood mononuclear cells of patients with mood disorders or schizophrenia and of blood donors. 981 43

RNA, extracted from peripheral blood mononuclear cells (PBMC) obtained from 81 Korean psychiatric patients (39 with schizophrenia, 33 with bipolar affective disorders and nine with major depression), was analyzed for a 391-nucleotide, highly conserved region of the p24 protein-encoding ORF II of Borna disease virus (BDV), using nested reverse transcription-polymerase chain reaction (RT-PCR). BDV genomic RNA was not detected in PBMC from any of the 81 Korean psychiatric patients. These data do not support an etiologic association between BDV infection and neuropsychiatric disorders in humans.
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PMID:Failure to demonstrate Borna disease virus genome in peripheral blood mononuclear cells from psychiatric patients in Korea. 1032 84

The prevalence of Borna disease virus (BDV)-specific antibodies among patients with psychiatric disorders and healthy individuals has varied in several reports using several different serological assay methods. A reliable and specific method for anti-BDV antibodies needs to be developed to clarify the pathological significance of BDV infections in humans. We developed a new electrochemiluminescence immunoassay (ECLIA) for the antibody to BDV that uses two recombinant proteins of BDV, p40 and p24 (full length). Using this ECLIA, we examined 3,476 serum samples from humans with various diseases and 917 sera from blood donors in Japan for the presence of anti-BDV antibodies. By ECLIA, 26 (3.08%) of 845 schizophrenia patients and 9 (3.59%) of 251 patients with mood disorders were seropositive for BDV. Among 323 patients with other psychiatric diseases, 114 with neurological diseases, 75 with chronic fatigue syndrome, 85 human immunodeficiency virus-infected patients, 50 with autoimmune diseases including rheumatoid arthritis and systemic lupus erythematosis and 17 with leprosy, there was no positive case except one case each with alcohol addiction, AIDS, and dementia. Although 19 (1.36%) of 1,393 patients with various ocular diseases, 10 (1.09%) of 917 blood donors, and 3 (4.55%) of 66 multitransfused patients were seropositive for BDV-specific antigen, high levels of seroprevalence in schizophrenia patients and young patients (16 to 59 years old) with mood disorders were statistically significant. The immunoreactivity of seropositive sera could be verified for specificity by blocking with soluble p40 and/or p24 recombinant protein. Anti-p24 antibody was more frequent than p40 antibody in most cases, and in some psychotic patients antibody profiles showed only p40 antibody. Although serum positive for both p40 and p24 antibodies was not found in this study, the p40 ECLIA count in schizophrenia patients was higher than that of blood donors. Furthermore, we examined 90 sera from Japanese feral horses. Antibody profiles of control human samples are similar to that of naturally BDV-infected feral horses. We concluded that BDV infection was associated in some way with psychiatric disorders.
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PMID:Detection of borna disease virus-reactive antibodies from patients with psychiatric disorders and from horses by electrochemiluminescence immunoassay. 1047 20

Despite considerable effort to identify susceptibility loci for schizophrenia, none have been localized. Multiple genome scans and collaborative efforts have shown evidence for linkage to regions on chromosomes 1q, 5q, 6q, 8p, 13q, 10p and 22q.(1-9) Heterogeneity is likely. We previously mapped schizophrenia susceptibility loci (SSL) to chromosomes 13q32 (P = 0.00002) and 8p21-22 (P= 0.0001) using 54 multiplex pedigrees and suggested linkage heterogeneity. We have now stratified these families based on co-segregating phenotypes in non-schizophrenic first degree relatives (schizophrenia spectrum personality disorders (SSPD); psychotic affective disorders (PAD)). Genome scans were conducted for these phenotypic subgroups of families and broadened affected phenotypes were tested. The SSPD group provided its strongest genome-wide linkage support for the chromosome 8p21 region (D8S1771) using either narrow (non-parametric lod (NPL) P= 0.000002) or broadened phenotypes (NPL P = 0.0000008) and a new region of interest on 1p was identified (P = 0.006). For PAD families, the peak NPL in the genome scan occurred on chromosome 3p26-p24 (P = 0.008). The identification of multiple susceptibility loci for schizophrenia may be enhanced by stratification of families using psychiatric diagnoses of the non-schizophrenic relatives.
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PMID:Genetic heterogeneity in schizophrenia: stratification of genome scan data using co-segregating related phenotypes. 1112 95

Borna disease virus (BDV) has been suggested to play a role in the etiology of schizophrenia. We tested the hypothesis that markers of BDV infection are more frequent in Surinamese immigrants to the Netherlands, diagnosed with schizophrenia, than in Dutch-born healthy subjects. For reasons that are poorly understood there is an increased incidence of schizophrenia in this immigrant group. Blood was obtained from 29 male schizophrenic patients (DSM-IV criteria) and from 26 healthy males. For detection of anti-BDV antibodies an indirect immunofluorescence assay (IFA) was performed. A nested, reverse-transcriptase-PCR, using primers specific for the p24 and p40 BDV genes, was used to determine BDV-RNA in peripheral blood mononuclear cells. Contrary to our expectations, the frequencies of BDV markers in the group of healthy subjects, as determined by IFA and both PCRs, exceeded that in the group of patients. The results do not support an association between markers of BDV infection in blood and schizophrenia. It is unlikely that the high incidence of schizophrenia in Surinamese immigrants is caused by BDV, but the small number of subjects examined do not warrant definitive conclusions.
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PMID:Borna disease virus and schizophrenia in Surinamese immigrants to the Netherlands. 1113 37


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