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 association between apolipoprotein E (ApoE) alleles and schizophrenia has remained controversial. A recent report claiming that ApoE epsilon3 Taiwan Chinese carriers have an increased risk of schizophrenia prompted us to investigate the allele frequency in a large group of Japanese schizophrenic patients. Serum samples were obtained from 314 schizophrenic patients and 188 controls in Japan and examined using isoelectric focusing/immunoblotting. There were no significant differences in ApoE allele frequencies between schizophrenic patients and controls and in the odds ratios for schizophrenia among the epsilon2, epsilon3 and epsilon4 carriers. In contrast to the report from Taiwan, our findings and results of the majority of previous studies suggest no effects of ApoE alleles on the development of schizophrenia.
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PMID:Apolipoprotein E epsilon3 allele is not a risk factor of schizophrenia: a study of 314 Japanese patients. 1094 Jul 61

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.
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PMID:Association study of apolipoprotein E epsilon4 with clinical phenotype and clozapine response in schizophrenia. 1109 31

The apolipoprotein E (APOE) epsilon4 allele is a known risk factor for the development of Alzheimer's disease, however, an association of the APOE genotype with schizophrenia is controversial. We investigated the association in 60 Korean schizophrenic patients and 60 healthy controls. APOE genotypes were identified by reverse hybridization-based line probe assay. There were significant differences in the distribution of APOE genotypes between schizophrenic patients and controls. APOE epsilon2 and epsilon3 allele frequencies in schizophrenic patients were significantly different from those in controls. Our results suggest that APOE alleles seem to be operative in the pathogenesis of schizophrenic disorders.
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PMID:Apolipoprotein E genotype in Korean schizophrenic patients. 1174 62

Five hundred and seventy nine Chinese patients with schizophrenia who met DSMIV criteria for the disorder were genotyped for alleles epsilon 2,3,4 of apolipoprotein E (APOE) gene. All were recruited from inpatients and outpatients attending a large mental health centre in Shanghai. Results were compared to APOE data on 1528 controls drawn from the same area. Major differences in APOE genotype ratios and allele frequencies were observed between the patients and controls. The patients with schizophrenia had highly significantly (p<0.0001) increased epsilon 4/-genotypes and allele frequencies, and decreased epsilon 3/3 genotypes and epsilon 3 allele frequencies compared to controls. The effect was independent of sex and/or age of onset of illness, but strongly influenced by date of birth. Significant differences were restricted to individuals with schizophrenia born either before 1949 or during the period 1958-1967. Both were times of severe food shortages and malnutrition. We suggest that APOE may operate as an additional risk factor for schizophrenia in individuals subjected to fetal and/or early postnatal malnutrition.
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PMID:Association of APOE gene with schizophrenia in Chinese: a possible risk factor in times of malnutrition. 1283 18

Two members of the family of low-density lipoprotein receptors (i.e., very low-density lipoprotein [VLDL] receptor and apolipoprotein E [apoE] type 2 receptor) are expressed in brain, where they bind and transduce reelin, a secreted glycoprotein that shares structural analogies with extracellular matrix proteins. In the developing fetal brain, reelin-signal transduction is critical for the correct positioning of neurons and the formation of appropriate synaptic connections, whereas in the mature brain, reelin participates in the mediation of experience-dependent synaptic plasticity. An important "downstream" consequence of the reelin-signal transduction cascade is inhibition of the phosphorylation of tau, a protein that regulates microtubule assembly and stability. Importantly, hyperphosphorylated tau comprises the paired helical filament, whose pathological deposition as neurofibrillary tangles is implicated in Alzheimer's disease; hyperphosphorylated tau is also implicated in the pathogenesis of other neurodegenerative disorders. Isoforms of apoE may affect the binding of reelin to its cell surface receptors and, thereby, influence tau phosphorylation, whereas insulin, insulin-like growth factor-1, and the lithium ion have actions within the cell at the level of the specific tyrosine kinases involved in the phosphorylation of tau. These data support the exploration of pharmacotherapeutic interventions designed to prevent or reduce the burden of hyperphosphorylated tau. Impaired reelin-signal transduction due to an actual deficiency of reelin expression may occur in at least some patients with psychotic disorders, especially schizophrenia; conceivably, hyperphosphorylation of tau would result from deficient transduction of reelin in schizophrenia. Schizophrenia has been conceptualized as a neurodevelopmental disorder of impaired synaptic "connectivity", whose consequence does not become fully apparent until late adolescence or early adulthood. In summary, hyperphosphorylation of tau may be an underlying point of pathological convergence for several neuropsychiatric disorders, and prevention of tau hyperphosphorylation may be an important therapeutic target.
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PMID:Dysregulation of tau phosphorylation is a hypothesized point of convergence in the pathogenesis of alzheimer's disease, frontotemporal dementia and schizophrenia with therapeutic implications. 1679 87

This study aims to find the biomarkers or associated proteins in body fluids of schizophrenia patients so that we can further understand the etiology of schizophrenia. We applied proteomic technologies combining two-dimensional electrophoresis with Coomassie blue staining and mass spectrometry and identified a procedure for the clinical screening of disease-influenced body fluid proteins in two sets of samples, plasma from 19 schizophrenia patients and cerebrospinal fluid (CSF) from 35 drug-treated schizophrenic patients and 36 healthy controls. The expression of transthyretin (TTR) tetramer increased significantly in plasma of schizophrenic patients after a valid 2 months in-hospital antipsychotic treatment. Conversely, the expression of the TTR tetramer and apolipoprotein E (ApoE) was down-regulated by up to 1.68 and 3.62 times, respectively, in the CSF of schizophrenia patients compared to that of normal controls, which has not been reported previously. Considering that the TTR tetramer and ApoE are both retinoid transporters, retinoid dysfunction might be involved in the pathology of schizophrenia.
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PMID:Dysregulation of retinoid transporters expression in body fluids of schizophrenia patients. 1708 Oct 74

Reelin, a secretory protease that plays major roles in neurodevelopment and synaptic plasticity, may also play a role in the pathogenesis of schizophrenia. The present study was undertaken to examine whether the expression of two receptors for reelin, very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor type 2 (ApoER2), were abnormal in peripheral blood lymphocytes of schizophrenic patients. In this study, we measured the mRNA levels of VLDLR and ApoER2 in blood lymphocytes from patients with schizophrenia (drug-naive patients (n=20) and medicated patients (n=20)) and age-and gender-matched healthy controls (n=40) using quantitative real-time RT-PCR. Furthermore, we examined the correlation between mRNA levels and clinical variables in patients. Levels of VLDLR mRNA in drug-naive, unmedicated patients with schizophrenia were significantly lower than those of controls. In contrast, levels of ApoER2 mRNA in drug-naive patients did not differ from those of controls, although the levels of ApoER2 mRNA in medicated patients were significantly lower than those of controls. Interestingly, levels of VLDLR mRNA in drug-naive patients showed significant increases with respect to baseline after six months of antipsychotic treatment, whereas levels of ApoER2 mRNA were significantly lower than baseline after six months of treatment. In all patients, there was a negative correlation between VLDLR mRNA levels and the severity of clinical symptoms. Our findings suggest that peripheral VLDLR mRNA levels may serve as a reliable peripheral biological marker of schizophrenia, and that the reelin-VLDLR/ApoER2 signaling pathway plays a role in the pathophysiology of schizophrenia.
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PMID:Decreased expression of reelin receptor VLDLR in peripheral lymphocytes of drug-naive schizophrenic patients. 1793 86

We have shown that plasma apolipoprotein E is significantly decreased in treatment-free subjects with schizophrenia spectrum and bipolar disorder but increases after treatment in bipolar disorder. Levels of apolipoprotein D were not changed by treatment. Hence changed apolipoprotein E could be involved in abnormalities in lipid homeostasis in some subjects with psychiatric diseases.
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PMID:Plasma apolipoprotein E is decreased in schizophrenia spectrum and bipolar disorder. 1809 47

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.
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PMID:Analyses of variants located in estrogen metabolism genes (ESR1, ESR2, COMT and APOE) and schizophrenia. 1816 2

Psychotic symptoms in Parkinson's disease (PD) are relatively common and, in addition to creating a disturbance in patients' daily lives, have consistently been shown to be associated with poor outcome. Our understanding of the pathophysiology of psychosis in PD has expanded dramatically over the past 15 years, from an initial interpretation of symptoms as dopaminergic drug adverse effects to the current view of a complex interplay of extrinsic and disease-related factors.PD psychosis has unique clinical features, namely that it arises within a context of a clear sensorium and retained insight, there is relative prominence of visual hallucinations and progression occurs over time. PD psychosis tends to emerge later in the disease course, and disease duration represents one risk factor for its development. The use of anti-PD medications (particularly dopamine receptor agonists) has been the most widely identified risk factor for PD psychosis. Other risk factors discussed in the literature include older age, disease severity, sleep disturbance, cognitive impairment, dementia and/or depression.Recent efforts have aimed to explore the complex pathophysiology of PD psychosis, which is now known to involve an interaction between extrinsic, drug-related and intrinsic, disease-related components. The most important extrinsic factor is use of dopaminergic medication, which plays a prominent role in PD psychosis. Intrinsic factors include visual processing deficits (e.g. lower visual acuity, colour and contrast recognition deficits, ocular pathology and functional brain abnormalities identified amongst hallucinating PD patients); sleep dysregulation (e.g. sleep fragmentation and altered dream phenomena); neurochemical (dopamine, serotonin, acetylcholine, etc.) and structural abnormalities involving site-specific Lewy body deposition; and genetics (e.g. apolipoprotein E epsilon4 allele and tau H1H1 genotype). Preliminary reports have also shown a potential relationship between deep brain stimulation surgery and PD psychosis.When reduction in anti-PD medications to the lowest tolerated dose does not improve psychosis, further intervention may be warranted. Several atypical antipsychotic agents (i.e. clozapine, olanzapine) have been shown to be efficacious in reducing psychotic symptoms in PD; however, use of clozapine requires cumbersome monitoring and olanzapine leads to motor worsening. Studies of ziprasidone and aripiprazole are limited to open-label trials and case reports and are highly variable; however, it appears that while each may be effective in some patients, both are associated with adverse effects. While quetiapine has not been determined efficacious in two randomized controlled trials, it is a common first-line treatment for PD psychosis because of its tolerability, ease of use and demonstrated utility in numerous open-label reports. Cholinesterase inhibitors currently represent the most promising pharmacological alternative to antipsychotics. Tacrine is rarely tried because of hepatic toxicity, and controlled trials with donepezil have not shown significant reductions in psychotic symptoms, due perhaps to methodological limitations. However, results from an open-label study and a double-blind, placebo-controlled trial involving 188 hallucinating PD patients support the efficacy of rivastigmine. With regard to non-pharmacological interventions, case reports suggest that electroconvulsive therapy has the potential to reduce psychotic symptoms and may be considered in cases involving concurrent depression and/or medication-refractory psychosis. Limited case reports also suggest that specific antidepressants (i.e. clomipramine and citalopram) may improve psychosis in depressed patients. Finally, studies in the schizophrenia literature indicate that psychological approaches are effective in psychosis management but, to date, this strategy has been supported only qualitatively in PD, and further studies are warranted.
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PMID:Pathophysiology and treatment of psychosis in Parkinson's disease: a review. 1866 59


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