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 cumulative evidence from over a century of research overwhelmingly implicates genes in the etiology of Schizophrenia. Twin studies consistently find higher rates of schizophrenia among cotwins of monozygotic compared with dizygotic twins and adoption studies show that familial transmission is mediated by genetic, not adoptive relationships. Nevertheless, the hunt for schizophrenia genes with molecular genetic technologies has been disappointing. Although the available literature suggests that cytogenetic abnormalities cause some cases of schizophrenia, these abnormalities must account for only a small fraction of all schizophrenia. Attempts to scan the entire genome with DNA markers spaced at regular intervals have failed to produce unequivocal linkage findings. Notably, several groups have reported findings suggestive of linkage to chromosome 22 and other work provides weak evidence of a gene on the sex chromosomes. The search for schizophrenia genes has been complicated by its unknown mode of transmission, the possibility of phenocopies and genetic heterogeneity.
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PMID:Genetic heterogeneity of schizophrenia. 750 24

Despite initial setbacks, linkage studies with DNA markers continue to occupy center stage in psychiatric research. Advances in molecular and statistical techniques have revived the search for disease genes, leading to a new harvest of findings. Most interest in recent years has focused on potential linkages between schizophrenia and chromosomes X-Y (the pseudoautosomal region) and 22q12-13.1, and between bipolar affective disorder and chromosomes 18 (pericentromeric region) and 21q22.3. This article provides a critical evaluation of theses studies, with implications for future research. Concerns over earlier linkage trials make this scrutiny current and topical.
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PMID:Genes and psychosis: old wine in new bottles? 757 64

Two of the favorite hypotheses of schizophrenia research-maldevelopment of cerebral cortex and malfunction of brain dopamine systems-have often seemed difficult to reconcile. This article reviews recent research that suggests a heuristically useful reconciliation centered on the functional neuroanatomical concept of prefrontal-temporolimbic cortical connectivity. Anatomical findings from postmortem studies and neuropsychological and neuroimaging studies of brain function in patients with schizophrenia have implicated a developmental 'dysconnection' of temporolimbic-prefrontal cortices. The possibility that such dysconnection can account for the principal phenomenology of the illness, including its delayed onset and its treatment, is suggested by neurologic disease analogies such as metachromatic leukodystrophy and by recent studies in animals with developmental cortical lesions. Studies mapping neuronal gene expression indicate that all antipsychotic drugs modulate DNA transcription in a region of the nucleus accumbens that receives converging inputs from prefrontal and temporolimbic cortices, suggesting that indirect compensation for dysfunctional communication between prefrontal and temporolimbic cortices is a therapeutic mechanism of these drugs. Treatments aimed at direct cortical compensation may be more effective.
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PMID:Cortical maldevelopment, anti-psychotic drugs, and schizophrenia: a search for common ground. 757 73

Recently, it has been demonstrated that unstable trinucleotide repeats are the etiologic factor in myotonic dystrophy, fragile-X syndrome, Kennedy's disease, Huntington's disease, spinocerebellar ataxia type 1, and dentatorubral-pallidoluysian atrophy. All available evidence suggests that these expanded trinucleotide repeats, or unstable DNA, are the biological basis of the clinical phenomenon of genetic anticipation. Two components of anticipation, increased severity and earlier age of onset in subsequent generations, have been widely observed in schizophrenia. We review the evidence for and against genetic anticipation in schizophrenia. Although the major criticisms of the anticipation hypothesis can be questioned, so can the evidence in favor of it. We conclude that molecular genetic approaches might be the most useful means of resolving ambiguity in clinical arguments about the origin of the anticipation-like phenomenon in schizophrenia.
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PMID:Genetic anticipation in schizophrenia: pro and con. 758 22

We report here linkage data on two families with multiple cases of schizophrenia originating from the genetically isolated population of Finland. We analyzed chromosomal DNA regions containing relevant candidate genes for schizophrenia and chromosomal regions which have been among the most widely studied in schizophrenia research due to associations between chromosomal anomalies and schizophrenia observed in certain families or populations. These include the chromosomal regions 5q11-q13, 11q and 15q21 as well as gene loci coding for components of dopamine, serotonin and amino acid transmitter pathways. No evidence for linkage to any of the chromosomal regions or candidate genes could be obtained, our data in fact suggested exclusion of all these regions as the site for major predisposing loci for schizophrenia in our families. On the 11p region the lod scores obtained deviated in the two families, but the difference remained statistically insignificant. The data emphasize the importance of analyzing families even with restricted genetic background separately since locus heterogeneity is likely to be detected not only between ethnic groups but also between diagnostic classes of the schizophrenia spectrum of diseases.
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PMID:Linkage analysis in two schizophrenic families originating from a restricted subpopulation of Finland. 771

Because antipsychotic drugs selectively block dopamine receptors and since dopamine D4 receptors are elevated sixfold in postmortem schizophrenia brain, we searched for possible abnormalities in the coding region of the genomic DNA sequence for the dopamine D4 receptor in control and schizophrenia tissues. The DNA sequence for the first 250 bases of exon 3 of this receptor was examined in the genomic DNA from 296 control individuals and 58 schizophrenics. Twenty-three out of 183 control blacks (12.6%) and 3 out of 24 (12.5%) schizophrenic blacks revealed a replacement of T by G, predicting a substitution of valine by glycine at amino acid position 194. The identical prevalence of 12.5% indicates that the variant is not associated with schizophrenia. The amino acid replacement occurs one amino acid away from a serine amino acid which is critical for the attachment of dopamine. None of the 147 Caucasians (113 controls; 34 schizophrenics) revealed this variant, termed D4GLYCINE194.
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PMID:Dopamine D4 receptor variant, D4GLYCINE194, in Africans, but not in Caucasians: no association with schizophrenia. 772 13

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

DNA manipulation techniques have allowed the isolation and identification of many genes which cause disease in man. The same techniques are now being automated, and are on the threshold of application to more common and more complex genetic predispositions to diseases such as diabetes and schizophrenia. This article outlines the technology behind this development, and discusses some of the social, legal and ethical difficulties that widespread screening for genetic traits will raise. It is argued that these issues must be considered now, so that considered social responses to this technology are in place in the five years it is likely to take to develop. The techniques of DNA manipulation that have led to recombinant proteins and biopharmaceuticals have also led to an unprecedented increase in understanding of human genetics, and a corresponding increase in the practical side of human genetics--medical genetic diagnosis. As a result, medical genetics is moving from a specialty of statisticians and cytologists into the mainstream of medicine, and will soon be the concern of every hospital, and probably of every GP. This offers huge benefits to patients, but also threatens misunderstanding and even the potential of abuse if this sophisticated understanding of our fundamental natures is used without precision.
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PMID:Medical genetics--genes and GPs for the 1990s. 776 15

In order to examine the molecular basis of schizophrenia we have employed a sequential differential hybridisation protocol to isolate mRNAs whose abundances are altered in schizophrenic compared to normal frontal cortex. Five cDNAs present at abnormal levels in the schizophrenic brain have been isolated by this method. The sequences were identified on the basis of homologies in the EMBL and Genbank databases. All the sequences encode mitochondrial transcripts; one encodes part of the 12s rRNA, three encode parts of the 16s rRNA region of the mitochondrial genome whilst the fourth encodes part of the amino acid sequence of cytochrome oxidase sub-unit II. It was established that mitochondrial sequences were not over-represented in the library and that this could therefore not account for the isolation of five mitochondrial transcripts by this procedure. Increased levels of cytochrome oxidase mRNA were detected in a further set of extracts from the frontal cortex of eight schizophrenic patients and five controls. The amount of mt-DNA was measured in these samples but there was no difference between schizophrenic and control. These results indicate a possible abnormality of mitochondrial function in the schizophrenic frontal cortex.
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PMID:A study of altered gene expression in frontal cortex from schizophrenic patients using differential screening. 776 31

Methods for localizing functional polymorphisms in candidate genes are important for the elucidation of pathogenesis in complex diseases such as schizophrenia and manic depression. Temperature gradient gel electrophoresis (TGGE), a variant of denaturing gradient gel electrophoresis (DGGE), can detect single-base mutations in a specified region of double-stranded DNA. This technique has been evaluated for use with polymerase chain reaction (PCR)-generated DNA fragments containing either transitional (A to G) or transversional (T to A) mutations. Single-base mutations of both types are detectable in PCR fragments up to 500 bp long. This method was then used to examine the coding region of the beta-nerve growth factor (NGF) gene for polymorphisms in PCR-generated DNA fragments derived from lymphocyte DNA of subjects with schizophrenia and normal subjects. No single-base mutations in sequence coding for the mature beta-NGF peptide were found in any of the subjects who were examined. If DNA sequence information is available for PCR primer design, TGGE detection of DNA polymorphisms can be used to rapidly determine whether or not a defect in a gene of interest contributes to the pathophysiology of the illness.
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PMID:Temperature gradient gel electrophoresis analysis of the beta-NGF gene in schizophrenia. 778 81


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