Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apolipoprotein E type epsilon 4 alleles are increased in both Alzheimer's disease (AD) and cortical Lewy body dementia, while the epsilon 2 allele has been associated as a protective factor against the development of dementia in AD. We have determined APOE genotype in schizophrenic patients coming to autopsy (age range 19-95 years). The allele frequencies in this group were: epsilon 2, 6.0%; epsilon 3, 67.9%; and epsilon 4, 26.2%. Three patients (14%) were homozygous for the epsilon 4 allele. Thus, schizophrenia is associated with an increased epsilon 4 allele frequency, as compared with controls (P = 0.01), that was indistinguishable from that found in either AD or Lewy body dementia. The increased epsilon 4 allele frequency was not associated with increased age of schizophrenia patient, indicating that it was not due to the co-existence of AD.
 ...
PMID:Apolipoprotein E type epsilon 4 allele frequency is increased in patients with schizophrenia. 878 41

Schizophrenic patients with the apolipoprotein E (APOE = gene; apoE = protein) epsilon4 allele exhibited lower psychosis scores than patients without the epsilon4 allele in previous reports. The present study tested the hypothesis that the APOE epsilon4 allele confers association with the clinical manifestations of schizophrenia or clozapine response. A total of 95 schizophrenic patients who were treatment resistant were included in the study. The results demonstrated that the presence of the APOE epsilon4 allele did not influence the response to clozapine in schizophrenic patients, neither was the baseline psychopathology related to the APOE epsilon4 allele. Given the multiple functions of the apoE protein in the brain, further study of the influence of APOE on CNS medication response is needed.
 ...
PMID:Association study of apolipoprotein E epsilon4 with clinical phenotype and clozapine response in schizophrenia. 1109 31

The epsilon 4 allele of APOE is generally accepted to be a risk factor in Alzheimer's disease and it has been related to other neuropsychiatric disorders, including schizophrenia. The results of several case-control studies have been inconclusive. To shed more light on this issue we carried out an association study that compared the APOE common variant in a group of 365 schizophrenia patients and 584 controls. We found no differences in the genotype distributions and allele frequencies of patients and controls. In the group of patients, we also analysed the possible influence of the epsilon 4 allele in the clinical variables. The most important findings are that the age at onset (AAO) of epsilon 4+ schizophrenic women, those that have one or two epsilon 4 alleles, is 4 years earlier than that of epsilon 4- women and their risk of suffering a negative syndrome subtype is four times greater. This was not found in schizophrenic men. Our results show that the APOE variant is not a risk factor for developing schizophrenia but that it may modulate its phenotypic expression in a sex-dependent manner.
 ...
PMID:Schizophrenic women with the APOE epsilon 4 allele have a worse prognosis than those without it. 1132 99

It has been suggested that genetic influences unmasked during neurodevelopment to produce schizophrenia may appear throughout neurodegeneration to produce AD plus psychosis. Risk of schizophrenia and psychosis in Alzheimer's disease (AD) has been linked to polymorphic variation at the dopamine receptor DRD3 gene implying similar causative mechanisms. We tested this association in a large cohort of Alzheimer's disease patients with a diagnosis of probable AD of 3 years or more duration from the relatively genetically homogenous Northern Irish population. We assessed relationships between genotypes/alleles of the DRD3 BalI polymorphism and the presence or absence of psychotic symptoms (delusions, hallucinations) in AD patients during the month prior to interview and at any stage during the dementia. No significant associations were found when delusions and hallucinations were cross-tabulated against S and G alleles and SS, SG and GG genotypes. Logistic regression failed to detect any influence of APOE, gender, family history or prior psychiatric history. In conclusion, we were unable to confirm previously reported associations between the DRD3 BalI polymorphism and psychotic symptoms in AD.
 ...
PMID:Psychotic symptoms in Alzheimer's disease are not influenced by polymorphic variation at the dopamine receptor DRD3 gene. 1534 29

Ninety-seven inpatients with tardive dyskinesia (average AIMS score = 13), the majority of whom were schizophrenic, were studied. Forty patients were Caucasian, and 57 were African-American. The APOE genotypes of these patients were compared to previously published genotypes of controls and with previously published studies of APOE genotypes in patients with schizophrenia. There were no significant differences in APOE allele frequencies comparing the African-American tardive dyskinesia population and the African-American control groups. In contrast, significant (< 0.05) P values were obtained comparing the Caucasian tardive dyskinesia population to the Caucasian controls, when comparing allele frequencies and genotypic frequencies. This study suggests that Caucasians bearing an APOE2 allele are at increased risk of developing tardive dyskinesia, whereas African-Americans are not. APOE genotype-specific risks of both tardive dyskinesia and Alzheimer's disease that vary across populations could be due to recruitment of patients or controls or could be due to modifying effects of differing genetic or environmental backgrounds. The mechanism by which the APOE2 allele increases risk of tardive dyskinesia is not known. Further information about the mechanisms of increased risk of tardive dyskinesia could result in stratification of prescribing practices weighing the costs of medications against the relative risk of side effects.
 ...
PMID:APOE2 allele increased in tardive dyskinesia. 1626 23

Optimal use of phenotype information is important in complex disease gene mapping. We describe a method, sequential addition, for the analysis of case-control data by taking into account of a quantitative trait that is measured in cases but not in controls. The method also provides an estimate of the best phenotype definition for future studies. We demonstrate proof of principle, using an example of incorporation of age-at-onset data into a study of a small sample for association between APOE and late-onset Alzheimer's disease. The sequential addition method finds evidence of association when conventional case-control methods fail. We also illustrate the use of the method for taking account of a dimensional measure of psychosis in a study of the schizophrenia susceptibility gene, dysbindin, in bipolar disorder.
 ...
PMID:Use of phenotypic covariates in association analysis by sequential addition of cases. 1653 25

Genetic factors have a variable impact on Alzheimer's Disease (AD), ranging from familial forms that are transmitted in an autosomal dominant fashion to sporadic AD, where a polygenic component is present. Most genes conferring susceptibility to AD are related to amyloid-beta deposition (APP; PS1; PS2; APOE; Cystatin-C; ubiquilin-1), oxidative stress (NOS2; NOS3) and inflammatory response (IL-1 alpha; IL-1 beta; IL-6; TNF-alpha). Genome-wide analyses, transcriptomics and proteomics approaches have pointed also to proapoptotic genes as increasing AD liability. Depression and psychotic symptoms that occur in a large proportion of AD patients have been associated with monoamine genes coding for metabolic enzymes (COMT), transporters (5-HTTLPR) and receptors (DRD1; DRD3). Genetic testing may be useful to confirm the diagnosis of AD in individuals with clinical signs of dementia, while it is generally not recommended as a predictive testing for AD in asymptomatic individuals. Drugs currently in use to treat AD are effective in only 20% of patients; their therapeutic effect is predominantly under genetic control (CYP26 gene; APOE). Environmental factors have been shown to moderate the effects of genes on psychiatric disorders such as depression, schizophrenia and ADHD. The study of gene-environment interactions in AD, that are still poorly understood, is essential to predict disease-risk in asymptomatic individuals. Genomics will provide a dynamic picture of biological processes in AD and new targets for the forthcoming anti-AD drugs.
 ...
PMID:Genetics of Alzheimer's disease. A rapidly evolving field. 1785 Nov 96

Relationships between gender, age-of-onset of schizophrenia and reproductive age strongly suggest a key role for gonadal hormones, and more specifically for estrogens, in the etiology of the illness. Also, estrogens act as neural growth and trophic factors influencing neuron and glial cells in many areas of the central nervous system. Therefore, we investigated the association between schizophrenia and 4 genes related to estrogen metabolism. These genes are ESR1 (estrogen receptor 1), ESR2 (estrogen receptor 2), APOE (apolipoprotein E) and COMT (catechol-O-methyltransferase). The expression of APOE and COMT, which contain estrogen response elements, have been demonstrated to be regulated by the estrogen receptors. In this current association study, we examined 59 single nucleotide polymorphisms (SNPs) located in the ESR1 (26), ESR2 (14), APOE (7) and COMT (12) loci. Allele frequencies were evaluated in the schizophrenia (n=585)-control (n=615) sample and no association was found with any of the four genes. In conclusion, our data suggest that the four analyzed genes do not play an important role in susceptibility to schizophrenia.
 ...
PMID:Analyses of variants located in estrogen metabolism genes (ESR1, ESR2, COMT and APOE) and schizophrenia. 1816 2

In an effort to pinpoint potential genetic risk factors for schizophrenia, research groups worldwide have published over 1,000 genetic association studies with largely inconsistent results. To facilitate the interpretation of these findings, we have created a regularly updated online database of all published genetic association studies for schizophrenia ('SzGene'). For all polymorphisms having genotype data available in at least four independent case-control samples, we systematically carried out random-effects meta-analyses using allelic contrasts. Across 118 meta-analyses, a total of 24 genetic variants in 16 different genes (APOE, COMT, DAO, DRD1, DRD2, DRD4, DTNBP1, GABRB2, GRIN2B, HP, IL1B, MTHFR, PLXNA2, SLC6A4, TP53 and TPH1) showed nominally significant effects with average summary odds ratios of approximately 1.23. Seven of these variants had not been previously meta-analyzed. According to recently proposed criteria for the assessment of cumulative evidence in genetic association studies, four of the significant results can be characterized as showing 'strong' epidemiological credibility. Our project represents the first comprehensive online resource for systematically synthesized and graded evidence of genetic association studies in schizophrenia. As such, it could serve as a model for field synopses of genetic associations in other common and genetically complex disorders.
 ...
PMID:Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database. 1858 79

The sequencing of the human genome and the identification of a vast array of DNA polymorphisms has afforded cognitive scientists with the opportunity to interrogate the genetic basis of cognition with renewed vigor. The extant literature on the molecular genetics of sustained and spatial attention is reviewed herein. Advances in our understanding of the neural substrates of sustained and spatial attention arising from the cognitive neurosciences can help guide putative linkages in cognitive genetics. In line with catecholamine models of sustained attention, associations have been reported between sustained attention and allelic variation in the dopamine beta hydroxylase gene (DBH), the dopamine D2 and D4 receptor genes (DRD2; DRD4) and the dopamine transporter gene (DAT1). Much evidence implicates the cholinergic system in spatial attention. Accordingly, individual differences in spatial attention have been associated with variation in an alpha-4 cholinergic receptor gene (CHRNA4). APOE-epsilon4 allele dosage has been shown to influence the speed of attentional reorienting in independent samples of nonaffected individuals. Preliminary evidence in both healthy children and children with attention deficit hyperactivity disorder (ADHD) suggests and association with variants of the DAT1 gene and the control of spatial attention across the hemifields. With the recent development of high-throughput genotyping techniques, such as microarrays, the time seems ripe for a genomewide association study that can identify quantitative trait loci (QTLs) for sustained and spatial attention. The identification of QTLs for attention will provide a range of novel candidate genes for disorders of attention, such as ADHD and schizophrenia, and will drive cognitive neuroscientists to understand how DNA variation influences the neural substrates of attention.
 ...
PMID:Molecular genetics of attention. 1859 81


1 2 3 Next >>