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)

Among relatives of Ashkenazi schizophrenic probands the rate of amyotrophic lateral sclerosis was 3/1,000, compared to expected population rates of approximately 2/100,000. Relative risk of bleeding disorders, including hematologic cancers, was increased more than three-fold compared to controls. Co-occurrence of motor neuron disease and blood dyscrasias, accompanied by psychosis, has long been recognized. A virally mediated autoimmune pathogenesis has been proposed. However, the familial co-occurrence of these three disease entities raises the possibility that the disease constellation be considered as a manifestation of a common underlying genetic defect. Such expansion of the spectrum of affectation might enhance the power of both candidate gene and linkage studies. Based on these findings the loci suggested as candidate regions in schizophrenia include a potential hot spot on chromosome 21q21-q22, involving the superoxide dismutase and amyloid precursor protein genes. Alternatively, genes on other chromosomes involved in the expression, transcription, or regulation of these genes, or associated with the illnesses of high frequency in these pedigrees are suggested. Candidates include the choroid plexus transport protein, transthyretin at 18q11.2-q12.1; the t(14;18)(q22;21) characterizing B-cell lymphoma-2, the most common form of hematologic cancer; and the 14q24 locus of early onset Alzheimer's disease, c-Fos, transforming growth factor beta 3, and heat shock protein A2. Expression of hematologic cancers and the suggested candidate genes are known to involve retinoid pathways, and retinoid disregulation has been proposed as a cause of schizophrenia.
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PMID:Elevated risks for amyotrophic lateral sclerosis and blood disorders in Ashkenazi schizophrenic pedigrees suggest new candidate genes in schizophrenia. 781 May 88

To limit genetic heterogeneity, this study focused on the widely extended pedigrees of Ashkenazi Jewish schizophrenic and autistic probands, to determine if similar causal mechanisms might obtain for both conditions. At least two previous epidemiological studies have demonstrated increased risk for schizophrenia in Ashkenazi Jews. The hypothesis posed is that increased prevalence of various rare autosomal recessive diseases among the Ashkenazim might contribute to the increased vulnerability to schizophrenia and to autism in this large genetic isolate. Rates of amyotrophic lateral sclerosis (ALS) and bleeding disorders were significantly increased among relatives of schizophrenic and autistic probands, compared to relatives of normal probands. These results suggest new candidate loci in schizophrenia and autism, particularly the chromosome 15q23-24 locus of the hexosaminidase A gene, causing various GM2 gangliosidoses, and the 21q22.1-q22.2 loci of the antioxidant, superoxide dismutase gene, and a cytokine receptor gene.
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PMID:A family history study of schizophrenia spectrum disorders suggests new candidate genes in schizophrenia and autism. 783 15

Dysregulation of free radical metabolism has been supposed to be involved in schizophrenia etiopathogeny. Recently, Wang et al. showed a red blood cell super oxide dismutase increase in positive schizophrenia (Crow's type I), but neither in negative schizophrenia (Crow's type II) nor in controls. The study included 28 in-patients suffering from acute positive psychosis who were compared with 15 controls. We confirmed the results of Wang. We found a significantly red blood cell Super oxide dismutase increase in positive psychosis, in comparison to negative psychosis and controls (p = 0.0001). This SOD increase was in relationship with the degree of clinical psychomotor excitement. After 21 days of neuroleptic treatment, SOD activity decreased and reached standard values. These results support the hypothesis of striking relationships between catecholaminergic hyper-metabolism and SOD increase, in positive psychosis. These could account for psychotic positive symptoms improvement with neuroleptic treatment, which blocks dopamine pathways.
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PMID:[Erythrocyte superoxide dismutase (eSOD) determination in positive moments of psychosis]. 787 2

There is increasing evidence that free radical-mediated CNS neuronal dysfunction is involved in the pathophysiology of schizophrenia. Free radicals (oxyradicals, such as superoxide, hydroxyl ions, and nitric oxide) cause cell injury when they are generated in excess or the antioxidant defense is impaired. Both of these processes seem to be affected in schizophrenia. Evidence of excessive oxyradical generation is premised on the assumption that there is increased catecholamine turnover, though there is little direct evidence to support such a view, which is further accentuated by neuroleptic treatment. However, antioxidant enzymes (superoxide dismutase, SOD; glutathione peroxidase, GSHPx; and catalase, CAT) which are constitutively expressed in all tissues, are found to be altered in erythrocytes of schizophrenic patients. Also, possible oxyradical-mediated injury to CNS is suggested by increased lipid peroxidation products in cerebrospinal fluid and plasma, and reduced membrane polyunsaturated fatty acids (PUFAs) in the brain and RBC plasma membranes. The brain is more vulnerable to oxyradical-mediated injury,because its membranes are preferentially enriched in oxyradical sensitive PUFAs, and damaged adult neurons cannot be replaced. In addition to their pathological role, oxyradicals have critical physiological functions in neuronal development, differentiation, and signal transduction, all of which may be altered in some cases of schizophrenia. It may be possible to define cellular injury processes, investigate underlying dynamic regulatory molecular processes, and find ways to prevent these injury processes using peripheral cell models, e.g., red blood cells, lymphocytes and cultured skin fibroblasts. Information on the clinical implications of these processes are valuable for developing new and innovative therapeutic strategies for schizophrenia.
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PMID:Free radical pathology and antioxidant defense in schizophrenia: a review. 914 91

Previous studies found peripheral activities of antioxidant enzymes to be abnormal in schizophrenic patients. It is not understood whether this is integral to the disease process or a result of long-term treatment with neuroleptics. Red blood cell activities of three antioxidant enzymes--superoxide dismutase, glutathione peroxidase, and catalase--were therefore examined in 14 drug-naive, first episode patients with a diagnosis of schizophrenia or schizophreniform disorder and 10 normal subjects. The patients had an average duration of psychosis of 4.46 days (SD 2.5). Superoxide dismutase activity was significantly lower in patients than in normal controls, with no difference between the groups in activities of the other two enzymes. Lower superoxide dismutase activity was associated with deterioration of school functioning from childhood to early adolescence and a history of poorer school functioning during early adolescence. These findings indicate a compromised antioxidant defense at the onset of psychosis, and suggest that oxidative injury might contribute to adverse developmental events in the pathogenic cascade of schizophrenia.
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PMID:Impaired antioxidant defense at the onset of psychosis. 914 92

Thirty-eight patients diagnosed as having continuous schizophrenia progrediens, 35 patients with shift-like schizophrenia and six patients with hypertoxic (feverish) schizophrenia were studied. The examinees displayed a marked increase in the blood content of lipid peroxidation products, such as malonic dialdehyde and conjugated dienes, together with an enhancement of the degree of erytrocytolysis, which events are particularly noticeable in hypertoxic- and continuous schizophrenia. Blood catalase activity gets higher, that of superoxide dismutase is on the decrease, which facts suggest to us some faults in the system of antioxidant defence.
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PMID:[The level of lipid peroxidation and the function of the antioxidant system in different forms of schizophrenia]. 979 17

Neuroanatomical studies of schizophrenia suggest that progressive neuropathological changes (such as neuronal atrophy and/or cell death) occur over the lifetime course of the disease. Early intervention with atypical neuroleptics has been shown to prevent progression of at least some symptoms, although the mechanisms by which neuroleptics may do this remain unknown. In this study, PC12 cells were used to determine the effects of the new atypical antipsychotic olanzapine on the gene expression of superoxide dismutase (SOD1) and the low affinity nerve growth factor receptor (p75). The results show that olanzapine increases SOD1 at concentrations of 10 and 100 microM after 48 hr of incubation in PC12 cultures. The treatment decreases p75 gene expression at concentrations 100 microM after 48 hr of incubation. Since both the upregulation of SOD1 mRNA and the antisense blockade of p75 mRNA have been associated with reduced cell death, our results suggest that olanzapine has neuroprotective potential and thus may be useful in preventing further neurodegeneration accompanying schizophrenia.
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PMID:Differential effects of olanzapine on the gene expression of superoxide dismutase and the low affinity nerve growth factor receptor. 1021 77

There has been increasing evidence that deranged superoxide dismutase (SOD) activities might be a risk factor for schizophrenia and/or tardive dyskinesia (TD). In the present study, we investigated the genetic association between a functional polymorphism (Ala-9Val) in the human manganese (Mn) SOD gene and schizophrenia or TD (192 schizophrenics: 39 with TD and 153 without TD; 141 controls). No significant differences in the allelic or genotypic distribution between schizophrenics and controls were observed. However, we did find a significant difference in genotypic distribution between schizophrenics with and those without TD (p =. 03). Moreover, decreased -9Ala (mutant) allele was found among patients with TD (p =.02; odds ratio = 0.29; 95% confidence interval = 0.10-0.83). In conjunction with previous findings of increased free radicals and decreased SOD activities in TD subjects, these results suggest that the -9Ala (high activity) MnSOD allele may play a role in protecting against susceptibility to TD in schizophrenics.
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PMID:Manganese superoxide dismutase gene polymorphism and schizophrenia: relation to tardive dyskinesia. 1088 43

Albumin and bilirubin are metal-binding proteins, shown to possess free radical scavenging properties, and may thus be selective antioxidants. In the present study we examined whether individual plasma antioxidants such as albumin and bilirubin, which significantly contribute to total antioxidant status (TAS), are reduced in patients with schizophrenia. We prospectively studied plasma antioxidant proteins, i.e. albumin and bilirubin, in male veteran schizophrenic patients using a within-subject, repeated measures, on-off-on haloperidol treatment design, as well as age- and sex-matched healthy volunteers. Male patients with schizophrenia either during haloperidol treatment (n=46) or in a drug-free condition (n=35) had significantly lower levels of both plasma albumin and bilirubin compared with age- and sex-matched healthy volunteers (n=31). Such reductions of plasma antioxidant proteins in schizophrenic patients appear to be age-related changes, in contrast to those observed in healthy volunteers. On the other hand, levels of plasma albumin and bilirubin were not significantly affected by haloperidol treatment, haloperidol withdrawal, or length of drug-free period. Moreover, plasma TAS was not influenced significantly by cigarette smoking, even though it may selectively decrease plasma bilirubin but not albumin levels. The present findings, taken together with our previous results of reduced plasma TAS and uric acid, as well as an increased Red blood cell superoxide dismutase, lend further support to the hypothesis that a defect in the antioxidant defense system exists in schizophrenia that may lead to oxidative damage.
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PMID:Abnormal age-related changes of plasma antioxidant proteins in schizophrenia. 1116 86

The purpose of the study was to evaluate the effect of the classic antipsychotic haloperidol plus extract of ginkgo biloba (EGb) on treatment-resistant chronic schizophrenia and on blood superoxide dismutase (SOD) levels. Eighty-two patients with chronic refractory schizophrenia were studied. Forty-three patients were treated with haloperidol plus extract of ginkgo biloba (group 1), and 39 received haloperidol plus placebo (group 2). SOD levels of these patients were measured before and after treatment and were compared with SOD levels of 30 healthy volunteers. Therapeutic efficiency was equated with a change in clinical rating scores assessed by standardized measurement tools that included the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms (SANS) over this period. Patients in group 1 improved significantly as demonstrated by scores from these two assessment instruments; those in group 2 improved significantly only as shown by scores on SANS. SOD levels before treatment in all patients were significantly higher than those in healthy controls; after treatment, the SOD level decreased significantly in group 1 but not in group 2. These results suggest that EGb may enhance the efficiency of the classic antipsychotic haloperidol in patients with schizophrenia, especially on their positive symptoms, and that EGb may work through an antioxidant effect that is involved in the therapeutic mechanism in patients with chronic refractory schizophrenia.
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PMID:The effect of extract of ginkgo biloba added to haloperidol on superoxide dismutase in inpatients with chronic schizophrenia. 1119 54


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