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)

1. A number of antigens of the HLA system showed significant associations with clinical phenotypes of schizophrenia and manic depressive disorders. Even though we emphasize the need to consider these results with caution, we suggest that the findings now available indicate that the chromosomal regions which control the HLA system also contain the genetic material related to schizophrenia. On the other hand, although initial results have been encouraging, more work is needed before we can draw definite conclusions about the relationships between HLA antigens and the genetics of manic depressive disorders. All this recently acquired information is discussed and new lines for research are also suggested, including linkage studies in families, which might offer a more precise understanding of the genetic contribution to psychopathology. 2. Stressed also is the possibility that HLA determinants interfere with the interaction between neurotransmitters and/or psychotropic drugs and specific receptors. In this light, the clinical implications of HLA-A1 reactions to chlorpromazine and haloperidol, and of the HLA-A1 cross-reacting antigens are analyzed. Such studies are as yet very preliminary; however they perhaps help to clarify both the real biological roles of these antigenic membrane structures and the mechanisms by which psychotropic drugs interact with membrane receptors.
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PMID:HLA system, psychiatry and psychopharmacology. 40 35

The distribution of HLA-A-, B- -and -C-locus antigens was tested in 200 male patients with final diagnosis of schizophrenia. A significant increase of HLA-A28 and HLA-Cw4 antigens and haplotype A10--B18 was found. Indications were obtained for the increase of HLA-A1 in hebephrenic patients. It was presumed that the increase of CW4 represents the common denominator of the diverse findings on paranoid schizophrenia. The increase of CW4 indicates that the paranoid schizophrenia disease susceptibility locus is either the C locus itself or another closely linked locus (or loci). This would stress the importance of the HLA 'central' regions for HLA and disease associations. A hypothesis is presented which points to the possibility that HLA antigens could be genetic markers of three ethiopathogenetic subgroups of schizophrenia. The possible tests of this hypothesis are also suggested.
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PMID:HLA antigens as possible markers of heterogeneity in schizophrenia. 69 Apr 74

Chlorpromazine has been reported to interfere with the action of alloantibodies directed against HLA-A1. We attempted to replicate this finding using peripheral blood lymphocytes from 3 healthy donors in a complement-mediated lymphocytotoxicity assay. We were unable to find evidence of interference between chlorpromazine and the anti-HLA sera tested. Possible reasons for the difference between our finding and the previous report, as well as the implications for schizophrenia, are discussed.
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PMID:Failure to find interference between anti-HLA antibodies and chlorpromazine. 232 24

Studying families of schizophrenic patients, we observed that the risk of developing the overt form of the illness could be enhanced by some factors. Among these various factors we focused our attention on a biological variable, namely the presence or the absence of particular HLA antigens: partitioning our schizophrenic patients according to their HLA structure (i.e. those with HLA-A1 or CRAG-A1 antigens and those with HLA-non-CRAG-A1 antigens, respectively), revealed different illness distribution in the two groups. From a genetic point of view, this finding suggests the presence of heterogeneity in the hypothetical liability system related to schizophrenia and we evaluated the heterogeneity hypothesis by applying alternative genetic models to our data, trying to detect more biologically homogeneous subgroups of the disease.
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PMID:Genetic modelling in schizophrenia according to HLA typing. 349 Sep 34

We found no convincing association of HLA-antigens and Schizophrenia with exception of a significant reduction of Aw19 in our study of 140 schizophrenic patients. The incidence of the haploids HLA-AI,B7, -A2,B18, -A2, Bw35, -A3,Bw35, -A1,Cw3, -A2,Cw3 has been significantly increased and the haploids HLA-A1,B8, -A2,B5, -A2,B7, -A2,Cw2, -B12,Cw4, -B27, Cw2 significantly decreased compared with normals. HLA-A1,B8, -A2,B5, -A2,B7, -A2,Cw2, -B12,Cw2 have shown an important imbalance of the alleles possibly induced by the lowered fertility and migration of schizophrenic patient.
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PMID:[HLA-antigens in the diagnosis and genetics of schizophrenia]. 694 5

We found an increased lymphocyte proliferation after stimulation with an antigen "cocktail" in 49 schizophrenic patients and 37 patients suffering from affective psychosis, compared with 45 healthy control subjects. On the basis of this and other findings such as increased numbers of CD3+ and CD4+ cells, an increased ratio of CD4+/CD8+ cells, and a reduced level of suppressor cell activity in schizophrenia and endogenous depression, we investigated the influence of the human leukocyte antigen-Class I (HLA-A, HLA-B, HLA-C) system on the altered immune function and evaluated the relationship to immune function of a family history of psychiatric disorders. A cluster analysis of cases with regard to the HLA-Class I antigens was first performed in a group of 133 healthy control subjects, and two immunogenetically different clusters were found; then 86 patients (49 schizophrenics, 37 affective psychoses) for whom immune functional data were available were assigned to the two HLA-I clusters that had been determined in the control subjects. Analyses of variance (ANOVAs) showed no differences in immune function between the two clusters. With respect to the cluster assignment and the family history of psychiatric diseases, a two-way ANOVA revealed significant differences in the lymphocyte response to the antigen cocktail, in the number of CD8+ cells, and in one suppressor cell assay. When patients were compared by ANOVA on the basis of family history of psychiatric disorder, patients with a positive family history showed a significantly higher number of CD4+ cells and a higher CD4+/CD8+ ratio. Moreover, certain HLA genes, especially HLA-A1, HLA-B8, HLA-B16, and HLA-C2 seemed to be related to the immune function and/or to the immune function and the family history.
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PMID:Cellular immunity, HLA-class I antigens, and family history of psychiatric disorder in endogenous psychoses. 827 43

Susceptibility to autoimmunity is strongly influence by genes clustered in the MHC region, particularly class I and class II antigens. It has been proposed that there is an immune component in the aetiology of schizophrenia, and the distribution of human leukocyte antigens (HLA) in schizophrenic patients and controls has been investigated in numerous studies. Positive associations have been reported between schizophrenia and the HLA-A1, A2, A9, B5, Cw4, and DR8 and negative associations with HLA-DR4 and HLA-DQbeta*0602. Small sample size, variable diagnostic methodology, unreliable laboratory and statistical procedures, and possible mismatching of cases and controls may have contributed to a lack of consistency of results to date. Therefore, in this investigation we used a large and carefully diagnosed homogeneous Irish familial schizophrenic sample compared with ethnically matched controls. All alleles were determined using polymerase chain reaction amplification followed by short specific oligoprobes. We found no evidence of association with 80 HLA alleles (some previously not examined) from 4 genes. Our data therefore do not support the involvement of these classical HLA loci in the aetiology of schizophrenia at least in these Irish families. The remaining classical HLA loci (HLA-B and HLA-C) should be typed when reliable DNA-based methods become available.
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PMID:Schizophrenia and HLA: No association with PCR-SSOP typed classical loci in a large Irish familial sample. 1040 12

Several studies indicate an association between human leukocyte antigens (HLA) and clozapine-induced agranulocytosis. The authors have previously reported a significantly increased frequency of HLA-A1 among patients with schizophrenia who do not respond to conventional drugs, but do respond to clozapine treatment. In this study, the authors addressed the question of whether the same association is found in patients developing granulocytopenia or agranulocytosis. The frequency of the HLA-A1 allele in patients with clozapine-induced agranulocytosis or granulocytopenia was low (11.5%), whereas HLA-A1 was associated with a good therapeutic response to clozapine at an allele frequency of 58%. The frequency of HLA-A1 is 20% in the Finnish population. These results suggest that HLA-A1 may predict a good therapeutic outcome and a low risk of agranulocytosis and, thus, enable defining a subgroup of patients with schizophrenia in whom clozapine treatment could be started early to stop the disease from progressing.
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PMID:Mitchell B. Balter Award. Human leukocyte antigen-A1 predicts a good therapeutic response to clozapine with a low risk of agranulocytosis in patients with schizophrenia. 1119 46