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)

A set of schizophrenic male monozygotic triplets is described. At age 20 years, within 8 months the three men independently developed acute fulminant schizophrenic disorders (DSM-III-R) with auditory hallucinations, bizarre delusions, and thought disturbances. There were also great similarities between the triplets with regard to the chronic intermittent course of the disorder, impairment of social adjustment, and loss of working ability. The psychoses responded rapidly to conventional neuroleptic treatment. Neuropsychological assessment demonstrated similar marked reductions of attentional, mnestic, and executive functions. Magnetic resonance imaging (MRI) showed similar borderline ventricular enlargement and widened subarachnoid spaces over frontoparietal and basal regions as well as around the pituitary gland (empty sella). All the boys also had a right-sided hearing defect with a marked reduction of the ossicular bones on the right side. Possible clues as to etiological mechanisms were the lack of reported family history for the disorder and a possible influenza infection in the mother during the first trimester. It is suggested that a DNA aberration being present or occurring at conception initiated a precise time-programmed series of events that produced the very similar schizophrenic phenotypes. Such an aberration might have been induced by an external agent, occurred spontaneously, or been inherited by a recessive mechanism. It seems possible that the psychoses, the reductions of neuropsychological functions, the morphological MRI changes, and the right-sided ossicular reductions may all be related to such a DNA alteration.
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PMID:A set of male monozygotic triplets with schizophrenic psychoses: nature or nurture? 778 6

There is strong evidence for a genetic component in schizophrenia but its precise nature remains unclear. Positional cloning and studies of potential candidate genes offer prospects for progress. The diagnosis of schizophrenia can now be made reliably but questions remain over the most valid phenotypic definition. To deal with this and uncertainties regarding mode of transmission a 'polydiagnostic' approach is advisable. A wealth of new DNA markers has enhanced the potential for linkage studies which have so far focused on large multiply-affected families. Multi-centre collaborative studies that are currently under way are likely to identify genes of major effect but other strategies are required if it turns out that most cases result from the combined effect of multiple genes.
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PMID:The molecular genetics of schizophrenia. 780 84

The recent discovery that expanding trinucleotide repeats are a form of mutation is a radical departure from the traditional genetic principles of inheritance based on the stable transmission of DNA sequences. The concept that a gene may be altered from tissue to tissue in a single individual or from one generation to the next and that it may confer increasing mutability on itself has provided some insight into the phenomenon of anticipation as manifested by increasing severity, declining age of onset, and increasing penetrance in several inherited disorders. This concept raises the question of how common this mutational mechanism may be in the causes of genetic disease. For example, expansions of trinucleotide repeats may be the underlying mechanism for other disorders that show features suggestive of anticipation such as schizophrenia, bipolar affective disorder, autism and other hereditary ataxias. Expressed genes with trinucleotide repeats have been observed in fetal and adult brains. A recent approach to identifying expanded repeats may simplify the process of finding candidate genes. It is intriguing to speculate how often observations such as intrafamilial variation and even new mutations may be due to such a mechanism. Systematic studies of families with disorders found to be associated with such repeats will be necessary. The implications in genetic counseling for prediction of postnatal outcome as well as risks of recurrence are truly staggering. Meanwhile, the immediate benefit of the knowledge of trinucleotide repeat expansions concerning the six disorders discussed will be the application of direct methods of diagnosis avoiding linkage analysis. The long-term benefits may very well be the discovery of more effective treatment modalities based on correction of the gene defects. Exciting times for human genetics appear to be at hand.
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PMID:Genetic anticipation. Expanding tandem repeats. 784 37

Our work investigates the relationship between genetic factors and schizophrenia, seeking to identify a gene or genes associated with the clinical form of the disease in a group of Italian patients. In pursuit of the 'dopaminergic hypothesis' of schizophrenia, we explored a possible etiologic role of two dopamine receptor genes, DRD3 and DRD4, that have been repeatedly suggested as factors in the pathophysiology of the disease. We typed DNA polymorphisms in each of the genes that code for variation in the amino acid sequence of the receptor protein. An innovative design using parental chromosomes as controls--the 'haplotype relative risk' strategy--represents a significant improvement over previous association studies in psychiatric genetics. Our results suggest that, at least in our well-defined population, the candidate genes DRD3 and DRD4 do not appear to play a major role in the genetic etiology of schizophrenia.
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PMID:An association study between schizophrenia and the dopamine receptor genes DRD3 and DRD4 using haplotype relative risk. 786 86

An association of HLA-DR8 and DR1 with DSM-III schizophrenia has been reported in Japan (Miyanaga et al. (1984) Biol. Psychiatr. 19, 121-129). To further investigate this preliminary finding, we compared HLA-DR types in 44 unrelated Japanese schizophrenics (DSM-III-R) with those in 51 unrelated, healthy Japanese volunteers. Group-specific PCR amplification was used in the determination of HLA-DR in the patients. No significant difference was observed in the frequency of any DR types between patients and controls, after statistical correction for multiple testing. However, the frequency of DR1 in our patients (23%) and controls (10%) was almost the same as those in the previous report (22% vs. 10%), which means that there is a suggestive trend which could become significant if numbers were larger. It is argued that an exact determination of HLA-DR by DNA typing is important in current HLA studies of schizophrenia.
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PMID:HLA-DR types in Japanese schizophrenics: analysis by group-specific PCR amplification. 789 26

The dystrophin gene, located at chromosome Xp21, was evaluated as a candidate gene in chronic schizophrenia in response to the report of a large family in which schizophrenia cosegregated with Becker muscular dystrophy [Zatz et al., 1991: Am J Hum Genet 49: A364; 1992: J Med Genet 30(2):131-134]. Genomic DNA from 94 men with chronic schizophrenia was evaluated by Southern blot analysis using cDNA probes that span exons 1-59. No exonic deletions were identified. An unexpectedly high rate of polymorphism was calculated in this study and two novel polymorphisms were found, demonstrating the usefulness of the candidate gene approach even when results of the original study are negative.
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PMID:Screening the dystrophin gene suggests a high rate of polymorphism in general but no exonic deletions in schizophrenics. 790 88

A collaboration involving four groups of investigators (Johns Hopkins University/Massachusetts Institute of Technology; Medical College of Virginia/The Health Research Board, Dublin; Institute of Psychiatry, London/University of Wales, Cardiff; Centre National de la Recherche Scientifique, Paris) was organized to confirm results suggestive of a schizophrenia susceptibility locus on chromosome 22 identified by the JHU/MIT group after a random search of the genome. Diagnostic, laboratory, and analytical reliability exercises were conducted among the groups to ensure uniformity of procedures. Data from genotyping of 3 dinucleotide repeat polymorphisms (at the loci D22S268, IL2RB, D22S307) for a combined replication sample of 256 families, each having 2 or more affected individuals with DNA, were analysed using a complex autosomal dominant model. This study provided no evidence for linkage or heterogeneity for the region 22q12-q13 under this model. We conclude that if this region confers susceptibility to schizophrenia, it must be in only a small proportion of families. Collaborative efforts to obtain large samples must continue to play an important role in the genetic search for clues to complex psychiatric disorders such as schizophrenia.
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PMID:Follow-up of a report of a potential linkage for schizophrenia on chromosome 22q12-q13.1: Part 2. 790 90

We initiated a genome-wide search for genes predisposing to schizophrenia by ascertaining 9 families, each containing three to five cases of schizophrenia. The 9 pedigrees were initially genotyped with 329 polymorphic DNA loci distributed throughout the genome. Assuming either autosomal dominant or recessive inheritance, 254 DNA loci yielded lod scores less than -2.0 at theta = 0.0, 101 DNA markers gave lod scores less than -2.0 at theta = 0.05, while 5 DNA loci produced maximum lod scores greater than 1: D4S35, D14S17, D15S1, D22S84, and D22S55. Of the DNA markers yielding lod scores greater than 1, D4S35 and D22S55 also were suggestive of linkage when the Affected-Pedigree-Member method was used. The families were then genotyped with four highly polymorphic simple sequence repeat markers; possible linkage diminished with DNA markers mapping nearby D4S35, while suggestive evidence of linkage remained with loci in the region of D22S55. Although follow-up investigation of these chromosomal regions may be warranted, our linkage results should be viewed as preliminary observations, as 35 unaffected persons are not past the age of risk.
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PMID:Genomic scan for genes predisposing to schizophrenia. 790 92

Previous results of a genome-wide survey for schizophrenia susceptibility genes in nine multiplex families indicated a possible region of linkage on chromosome 22. We therefore tested for linkage using ten highly polymorphic chromosome 22 DNA markers. Lod score analyses were suggestive of linkage for several markers on the distal end of the chromosome; however, no lod score exceeded 3 assuming either autosomal dominant or autosomal recessive transmission. The highest lod score was 2.09 (theta = 0.10) for marker D22S276 under autosomal recessive inheritance. Based on simulation analyses, this result is unlikely to represent a false positive. Analyses using information from affected individuals only resulted in reduced lod scores, with a maximum of 1.40 (theta = 0.05) for D22S276 assuming autosomal recessive inheritance. Two nonparametric methods, sib pair analysis and the Affected-Pedigree-Member method, also yielded suggestive but inconclusive findings; results were positive, but strict thresholds of significance were not met. Additionally, we tested one candidate gene, the Arylsulfatase A gene, located in the region of 22q13.31-qter. Results were again inconclusive, though the DNA marker available for this gene was a 2-allele RFLP with heterozygosity of 0.5, and therefore not maximally informative. Further investigation of this chromosomal region and this and other candidate genes may be warranted.
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PMID:Analysis of chromosome 22 markers in nine schizophrenia pedigrees. 790 93

We used 10 highly informative DNA polymorphic markers and genetic linkage analysis to examine whether a gene locus predisposing to schizophrenia is located on chromosome 22, in 105 families with schizophrenia and schizoaffective disorder. The LOD score method, including analysis for heterogeneity, provided no conclusive evidence of linkage under a dominant, recessive, or penetrance free model of inheritance. Affected sib-pair analysis was inconclusive. Affected pedigree member analysis gave only suggestive evidence for linkage. Multipoint APM analysis, using 4 adjacent loci including D22S281 and IL2RB, a region of interest from the APM analysis, gave non-significant results for the three different weighting functions.
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PMID:Search for a schizophrenia susceptibility locus on human chromosome 22. 807 69


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