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 genetic case-control study was conducted in a group of patients with schizophrenia (n = 67; DSM-III) and psychiatrically normal controls matched for ethnicity (n = 84), living in the same geographical area. Using three different DNA polymorphisms of the gene encoding porphobilinogen deaminase (PBGD), a candidate gene for schizophrenia, an association with schizophrenia could not be detected. No significant associations were detected even after sub-division of the cohort by ethnicity and by gender.
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PMID:Schizophrenia and porphobilinogen deaminase gene polymorphisms: an association study. 135 85

An association study of restriction fragment length polymorphisms (RFLPs) in the porphobilinogen deaminase (PBGD) gene and schizophrenia was conducted. RFLPs detected by MspI, PstI, ApaLI and BstNI in intron 1 of the gene were studied in 49 patients and 79 controls. There were no significant differences between the groups in allele frequencies, genotype counts or haplotype distribution.
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PMID:No association between RFLPs at the porphobilinogen deaminase gene and schizophrenia. 135 82

The dopamine hypothesis is one of the major etiological hypotheses of schizophrenia. The well-established role of genetic factors in schizophrenia together with reports of increased D2 dopamine receptor densities in untreated schizophrenic patients support the D2 dopamine receptor gene as a strong candidate gene for schizophrenia. The recent cloning of the D2 dopamine receptor gene made it possible to test the involvement of the D2 dopamine receptor locus (DRD2) in a large Swedish and a smaller Californian schizophrenia pedigree. Using multipoint linkage analysis between schizophrenia and a genetic map that includes the DRD2 locus and assuming a dominant mode of inheritance, we were able to exclude the DRD2 locus with a lod score of -4.14 for the penetrance of 0.72 and with a lod score of -3.05 for the lower bound penetrance of 0.56. The area of exclusion (lod score, less than -2.00) extended 27 centimorgans. These results provide strong evidence against linkage of the D2 dopamine receptor gene region to schizophrenia in the two pedigrees investigated. We conclude that the genetic predisposition to schizophrenia in these pedigrees is not due to aberrations in the DRD2 locus or the porphobilinogen deaminase locus. Our results do not support the D2 dopamine receptor hypothesis of schizophrenia. However, they cannot exclude the possibility that other genes regulating aspects of D2 dopamine expression might be involved in the etiology of schizophrenia, such as the expression of two D2 dopamine receptor subtypes by alternative RNA splicing.
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PMID:No linkage between D2 dopamine receptor gene region and schizophrenia. 206 95

All cases of acute intermittent porphyria (AIP) are believed to be caused by a mutation in the gene encoding for porphobilinogen deaminase, a rate-limiting enzyme in the haem synthetic pathway. This gene has been mapped to the long arm of chromosome 11, a region of the genome that has recently attracted considerable attention as a possible location for genes implicated in major mental disorder. This study was designed to show whether major mental illness co-segregated with acute intermittent porphyria in families where the two conditions are found. The study also investigated the relation between clinical mental symptoms and biochemical parameters of acute intermittent porphyria. The case records of 344 consecutive patients admitted to the Porphyrias Research Group in the Western Infirmary in Glasgow between 1950 and 1988 with acute intermittent porphyria were examined for evidence of psychiatric contact. Of 16 individuals identified, 12 were available for the study. Forty relatives of these 12 probands, including 9 who were asymptomatic carriers of AIP, were interviewed for lifetime history of mental illness and current symptoms. Comparisons were made between 4 groups of patients based on urinary porphyrin levels and erythrocyte enzyme activity; 1) manifest acute intermittent porphyria, 2) latent acute intermittent porphyria, 3) normal relatives and 4) total acute intermittent porphyria (latent and manifest combined). No association was found between AIP and schizophrenia or manic-depressive illness. Only one patient with schizophrenia was found in the sample of 344 case notes, and in 2 families bipolar illness was found but did not segregate with acute intermittent porphyria. The commonest psychiatric diagnosis in patients was generalized anxiety.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute intermittent porphyria and mental illness--a family study. 802 93

There is growing evidence that some genetic predisposition is important in the etiology of schizophrenia. We have sought to implicate a major gene by performing a candidate gene association study comparing the allele frequencies of seven restriction fragment length polymorphisms (RFLPs) at six loci in both a psychiatrically normal control group (N = 51) and an affected (schizophrenia or schizoaffective disorder) group (N = 55). Each group comprised Caucasians of northern European origin. The candidate areas (D5S39, D5S78, dopamine receptor D2 (DRD2), D11S29, porphobilinogen deaminase (PBGD), and D11S84) were selected on the basis of prior cytogenetic findings in schizophrenics, linkage studies, and/or implicated gene products. The presence of a polymorphic ApaLI site within the PBGD gene showed a significant association with the presence of illness (P = 0.02). The relative risk of possessing the allele with the ApaLI site was 2.10. No significant association was found with any of the six other RFLPs. Our data suggests that either the PBGD gene itself or an unknown gene linked to and/or in linkage disequilibrium with the PBGD locus predisposes some individuals to schizophrenia. Independent replication of these findings will be required to determine their relevance to schizophrenia.
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PMID:Association between genetic variation at the porphobilinogen deaminase gene and schizophrenia. 809 29

The long arm of chromosome 11 is of interest in schizophrenia research because of three independent reports of balanced 11q translocations cosegregating with schizophrenia and other major psychiatric illness in pedigrees. In addition, a number of candidate genes for psychosis are located in the translocated regions. These include the dopamine D2 receptor, porphobilinogen deaminase, which has shown an allelic association with schizophrenia, and neural cell adhesion molecule, a cell surface glycoprotein involved in neuronal cell-cell recognition during brain development. To search for a schizophrenia locus on chromosome 11q, we conducted linkage analyses in 12 multiplex pedigrees. Sixteen DNA markers, including the above three candidate genes, were used to screen the entire long arm of chromosome 11. None of these markers were supportive of linkage to schizophrenia regardless of whether the affected phenotype was defined narrowly or broadly, whether high or low penetrance was assumed. Both dominant and recessive models tested more than 130 centimorgans of chromosome 11q, and therefore, the reported translocation regions. The results provide no evidence for a susceptibility locus for schizophrenia on chromosome 11q in these pedigrees.
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PMID:A linkage study of chromosome 11q in schizophrenia. 843 42

We report the results of a collaborative linkage study using 12 polymorphic markers (9 loci) from the long arm of chromosome 11, and 24 families multiply affected with schizophrenia and other closely related disorders. This region is of interest because several families have been reported in which balanced translocations involving 11q apparently co-segregate with psychotic illness. In addition, the dopamine D2 receptor, porphobilinogen deaminase, and tyrosinase genes map within the region studied and may be aetiologically involved in schizophrenia. We have primarily analysed genotypic data by the LOD score method using a range of single gene models. In order to minimize error due to mis-specification of genetic parameters we have analysed data from markers at candidate gene loci by the non-parametric extended sib-pair method in addition to the LOD score method. Our results suggest that most of the region can be excluded from containing a gene of major effect in the aetiology of this disease.
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PMID:A linkage study of schizophrenia with DNA markers from the long arm of chromosome 11. 847 13

Acute intermittent porphyria mimics a variety of commonly occurring disorders and thus poses a diagnostic quagmire. Psychiatric manifestations include hysteria, anxiety, depression, phobias, psychosis, organic disorders, agitation, delirium, and altered consciousness ranging from somnolence to coma. Some patients develop psychosis similar to schizophrenia. Psychiatric hospitals have a disproportionate number of patients with this disorder as only difficult and resistant patients accumulate there. Presence of photosensitive porphyrins in the urine is diagnostic. When porphyrins are absent, excess of alpha aminolevulinic acid and porphobilinogen are present in the urine. The definitive test is to measure monopyrrole porphobilinogen deaminase in RBCs. This diagnosis should be entertained in the following situations: (a) unexplained leukocytosis; (b) unexplained neuropathy; (c) etiologically obscure neurosis or psychosis; (d) 'idiopathic' seizure disorder; (e) unexplained abdominal pain; (f) conversion hysteria, and (g) susceptibility to stress. Porphyria is important in psychiatry as it may present with only psychiatric symptoms; it may masquerade as a psychosis and the patient may be treated as a schizophrenic person for years; the only manifestation may be histrionic personality disorder which may not receive much attention. Diagnosis is based on a high index of suspicion and appropriate investigation. Various psychotropic drugs exacerbate acute attacks. While it is important not to use the unsafe drugs in porphyric patients, it is also imperative to look for this diagnosis in cases where these drugs produce unprecedented drug reactions.
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PMID:Porphyria: reexamination of psychiatric implications. 865 42

Acute intermittent porphyria (AIP) is the most common of the four forms of neuroporphyria. AIP mimics a variety of disorders and thus poses a diagnostic quagmire. Abdominal pain occurs in 90-95% of the attacks. Some patients develop psychiatric symptoms such as psychosis similar to schizophrenia. The diagnostic difficulty may lead to under-diagnosis of patients who present with strictly psychiatric symptoms. This assumption is supported by a high prevalence of AIP in psychiatric hospitals. Therefore, we encourage a high index of suspicion for AIP in psychiatric patients in order to prevent false psychiatric diagnosis. In addition we discuss psychotropic drugs that may exacerbate acute attacks in undiagnosed patients. We report a case in which the diagnosis of AIP was clouded by the presence of only psychiatric symptoms. The clue for diagnosis was an anamnestic detail of the use of a porphyrogenic drug prior to the admission. The diagnosis of AIP was supported by excess of alpha aminolevulinic acid (ALA) and porphobilinogen (PBG) in urine concomitantly with a decrease in porphobilinogen deaminase (PBGD) activity in erythrocytes. The diagnosis was further strengthened by the fact that the patient's father was identified as an AIP carrier. However, in the absence of typical organic symptoms of porphyria, one cannot definitely rule out the presence of schizophrenia in this patient in addition to AIR
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PMID:Acute intermittent porphyria: psychosis as the only clinical manifestation. 1691 Mar 86