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)

In addition to their ability to change the electrical properties of neurons, evidence suggests that neurotransmitters are able to alter the cell's metabolism. Transmitter phenotype is labile and expression might be regulated, during development, by the cellular environment of neurons. The study of a key enzyme in the synthesis of catecholamines, tyrosine hydroxylase (TH), has provided clues about these adaptive responses. This enzyme has a large molecular diversity, resulting from the differential splicing of its mRNA, which is tissue-specific and might result in long-term changes in activity of the enzyme and, therefore, in the availability of neurotransmitter at various synapses. The presence of different DNA sequences at the TH locus confers susceptibility to various disorders of the brain, including manic-depressive illness and schizophrenia. Indeed, an association between a rare variant allele of the gene encoding TH and the occurrence of schizophrenia has been found in several populations. New techniques being developed to treat diseases such as Parkinson's disease involve various gene therapies, including a method of transferring genes directly into nerve cells using an adenovirus-based system.
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PMID:The TiPS/TINS Lecture. Catecholamines: from gene regulation to neuropsychiatric disorders. 872 6

The human chromosomal band 6p23 is a Giemsa-negative (light) band that may be expected to be relatively gene rich. The genes for spinocerebellar ataxia type 1 (SCA1), guanosine monophosphate reductase (GMPR), DEK involved in a subtype of acute myeloid leukemia (AML), and the folate-sensitive fragile site FRA6A, have already been mapped to 6p23. Recent linkage data have suggested evidence for a susceptibility locus for schizophrenia in the region. We have constructed a single YAC contig of approximately 100 clones spanning the entire 6p23 band from 6p22.3 to 6p24.1 and covering 7.5-8.5 Mb of DNA. The YAC contig contains 55 markers including genetically mapped STSs, physically mapped STSs, anonymous STSs, anonymous ESTs, and ESTs from the genes mapped to the region. The order of the genetically mapped STSs is consistent with their order in the contig and some of the markers not resolved on the genetic map have been resolved by the YACs. Four of the YACs from 6p23 and covering approximately 3 Mb of DNA have been used to isolate approximately 300 cosmids from a flow-sorted human chromosome 6 cosmid library, which have been organized into pockets. The proposed susceptibility locus for schizophrenia is most closely linked to D6S260, which is located within the YAC contig along with genetic markers < or = 5 cM on either side. Therefore, the presented materials are valuable reagents for characterization of the genomic region implicated in schizophrenia.
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PMID:An integrated map of human chromosome 6p23. 875 Jan 94

Nineteen parent-offspring pairs obtained from 14 two-generation families with available medical records and diagnosis of schizophrenia were studied to compare the ages of onset of the parent generation with those of the offspring generation. The mean age of onset for the parent generation was 37.3 +/- 6.0 years and for the offspring generation was 20.8 +/- 4.4. The mean difference was thus 16.5 +/- 6.2, suggesting the occurrence of anticipation in schizophrenia (p < 0.001). Although some ascertainment biases (like reduced fertility in early-onset parents or early detection of symptoms in offsprings of affected parents) may partially contribute to the occurrence of anticipation, this study replicates recent reports of anticipation in several neuropsychiatric disorders, some of which have been shown to be associated with unstable expansions of trinucleotide repeats in the genomic DNA.
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PMID:Anticipation in Swedish families with schizophrenia. 875 Mar 61

Molecular genetics is helping define the contribution of genetic involvement in behavioral disorders. At this time, however, a severely limiting factor for DNA linkage studies of these disorders remains the definition of the phenotype. An example of this is found in the group of studies examining linkage of schizophrenia to the 5q location. Although various broad clinical interpretations of the schizophrenia phenotype were used to test for linkage, all but one study reported findings negative for linkage of schizophrenia to the 5q area. We offer a strategy based on family studies using segregation data of behavioral subtypes. We apply this strategy using molecular genetic technology to our study of psychopathology in patients. This approach offers the possibility of a clearer definition of the phenotype and is suggested for use in both linkage and association studies of neuropsychiatric disorders.
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PMID:Molecular genetics of psychopathologies: a search for simple answers to complex problems. 875 55

The term 'anticipation' is used to describe the increase in disease severity or the decrease in age of onset in succeeding generations within families. This phenomenon has been related to expansion of trinucleotide repeat DNA sequences in some genetic illnesses. We examined age of onset among two generations in familial schizophrenia. Twenty-six unilineal pedigrees previously ascertained for linkage studies were used. We defined the older generation as G1 and the younger generation as G2. Cumulative survival analysis for intergenerational pairwise comparisons in groups G1 and G2 showed a significantly earlier age of onset in G2 (10 years earlier). Additional analyses, which took into account some biases such as the censoring effect of age at interview and preferential ascertainment of late-onset parents, did not modify the results. No evidence for genomic imprinting was found in our sample. We conclude that anticipation occurs in our sample of familial schizophrenia.
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PMID:Further evidence for anticipation in schizophrenia. 877 Dec 17

In an attempt to understand schizophrenia, four important fields have been implicated in the disease process and are reviewed here. Early findings that antipsychotic drugs were dopamine antagonists led to a dopaminergic theory of schizophrenia. However, it now appears that a primary dopaminergic abnormality is an unlikely explanation. The cortex has always been thought to be involved in the development of schizophrenia and recent data from neuropsychological, postmortem and imaging studies have indicated that connections between the prefrontal and temporolimbic areas within the brain may be abnormal. Traditionally, schizophrenia has been considered to be a disease with an adult onset pathology. This theory has now been challenged by data suggesting that in schizophrenia, anatomical changes in the adult brain are non-progressive and occurred prior to the onset of illness. Finally, studies on neuronal gene expression have indicated that all antipsychotic drugs modulate DNA transcription in the shell of the nucleus accumbens and that newer antipsychotics produce a quite different pattern of expression from conventional neuroleptics. These recent approaches provide new opportunities in the understanding of schizophrenia, its treatment and prevention.
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PMID:Neurobiology of treatment-resistant schizophrenia: new insights and new models. 879 18

Anti-ribosomal P (anti-P) antibodies (IgG, IgA, IgM) were measured by an enzyme-linked immunosorbent assay (ELISA) in serial serum samples from the patients with systemic lupus erythematosus (SLE), and these clinical significance was investigated. Neuropsychiatric manifestations were observed in 24 of 144 patients with SLE. Twelve patients had lupus psychosis, nine convulsion or coma and three primary schizophrenia. In the group with lupus psychosis, serum C3 was significantly higher (p < 0.05) and anti-ds-DNA antibody was significantly lower (p < 0.05) than in the other patients. The titer of anti-P antibodies was significantly higher in the group with lupus psychosis than that of the other patients. In a longitudinal study, IgA and IgM classes of anti-P antibody were elevated at the onset of psychosis. The titer decreased following a remission of psychosis. Therefore, the measurement of immunoglobulin classes of anti-P antibody will be useful for the diagnosis and follow-up of patients with lupus psychosis.
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PMID:Neuropsychiatric manifestations in patients with systemic lupus erythematosus: diagnostic and predictive value of longitudinal examination of anti-ribosomal P antibody. 911 12

Evidence for genetic anticipation has recently become an important subject of research in clinical psychiatric genetics. Renewed interest in anticipation was evoked by molecular genetic findings of a novel type of mutation termed "unstable DNA." The unstable DNA model can be construed as the "best fit" for schizophrenia twin and family epidemiological data. We have performed a large-scale Southern blot hybridization, asymmetrical PCR-based, and repeat expansion-detection screening for (CAG)n/(CTG)n and (CCG)n/(CGG)n expansions in eastern Canadian schizophrenia multiplex families demonstrating genetic anticipation. There were no differences in (CAG)n/(CTG)n and (CCG)n/(CGG)n pattern distribution either between affected and unaffected individuals or across generations. Our findings do not support the hypothesis that large (CAG)n/(CTG)n or (CCG)n/(CGG)n expansions are the major etiologic factor in schizophrenia. A separate set of experiments directed to the analysis of small (30-130 trinucleotides), Huntington disease-type expansions in individual genes is required in order to fully exclude the presence of (CAG)n/(CTG)n- or (CCG)n/(CGG)n-type unstable mutation.
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PMID:Search for unstable DNA in schizophrenia families with evidence for genetic anticipation. 880 7

The expression of IgG and IgM autoantibodies directed against various autoantigens, either part of the central nervous system or not, was investigated in the sera of inpatients with schizophrenia (n = 10). An enzyme immunoassay was used to measure the levels of these autoantibodies in whole sera, IgG-depleted sera, and isolated IgG fractions. IgG and IgM antibodies, reacting with all the antigens tested, were present in the sera of patients with schizophrenia as well as in the sera of normal individuals. Among patients suffering from schizophrenia, IgM natural autoantibody reactivities could be higher (myoglobin, serotonin, tubulin), lower (dopamine), or even identical to those of normal individuals, depending on whether whole or fractionated sera were assayed and on the group of patients with schizophrenia (responders and nonresponders) considered. The isolated IgG fractions of patients suffering from schizophrenia had higher anti-DNA and antiserotonin reactivities than those detected in normal individuals.
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PMID:Differences in the natural autoantibody patterns of patients with schizophrenia and normal individuals. 882 Jan 73

A possible dysregulation of dopaminergic neurotransmission has been implicated in a variety of neuropsychiatric diseases. In the present study we systematically searched for the presence of mutations in the 5'-flanking region of the dopamine D1 receptor (DRD1) gene. This region has previously been shown to contain a functional promoter [Minowa et al., 1992: Proc Natl Acad Sci 89:3045-3049; Minowa et al., 1993: J Biol Chem 268:23544-23551]. We investigated 119 unrelated individuals (including 36 schizophrenic patients, 38 bipolar affective patients, and 45 healthy controls) using single-strand conformation analysis (SSCA). Eleven overlapping PCR fragments covered 2,189 bp of DNA sequence. We identified six single base substitutions: -2218T/C, -2102C/A, -2030T/C, -1992G/A, -1251G/C, and -800T/C. None of the mutations was found to be located in regions which have important influence on the level of transcriptional activity. Allele frequencies were similar in patients and controls, indicating that genetic variation in the 5'-regulatory region of the DRD1 gene is unlikely to play a frequent, major role in the genetic predisposition to either schizophrenia or bipolar affective disorder.
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PMID:Systematic screening for mutations in the 5'-regulatory region of the human dopamine D1 receptor (DRD1) gene in patients with schizophrenia and bipolar affective disorder. 883 16


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