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)

In order to examine antioxidant status and lipid peroxidation in schizophrenia patients, activities of three free radical scavenging enzymes (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)), and the level of thiobarbituric acid-reactive substances (TBARS) as an index of lipid peroxidation have been studied in red blood cells. Schizophrenic patients were divided into three groups (disorganized (n = 21), paranoid (n = 26) and residual types (n = 18)) to determine differences between subgroups. SOD, CAT and GSH-Px activities in the control group were found to be 1461.0 +/- 248.6 U g(-1) Hb, 148.2 +/- 59.3 k g(-1) Hb and 25.87 +/- 4.25 U g(-1) Hb, respectively. We found no significant differences in SOD activities between study and control groups. There was a significant increase in SOD activity in the residual group compared to the paranoid group (P < 0.005). CAT activity was found to be increased in disorganized (148%), paranoid (147%), and residual (165%) groups compared to the control group. GSH-Px activity was markedly increased in the study groups except the paranoid group. Statistically significant (3-4 fold) increases in TBARS levels of red blood cells were found in all the study groups. It is proposed that antioxidant status may be changed in schizophrenia and thus may induce lipid peroxidation. Therefore, oxidative stress may have a pathophysiological role in all the subtypes of schizophrenia.
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PMID:Evidence that the activities of erythrocyte free radical scavenging enzymes and the products of lipid peroxidation are increased in different forms of schizophrenia. 1124 87

The aetiopathogenesis of schizophrenia constitutes nowadays one of the major points of interest for researchers on this cosmopolitan disorder which involves about 1% of the world population and which significantly alters the social functioning of the individual. Numerous studies have focused on the role played by genome, environmental factors and biology in the development of symptoms. The neurodevelopmental theory is an illustration with the perinatal period considered as the main provider of environmental factors (hypertension, infections, bleedings during pregnancy, acute and chronic fetal distress.). Many authors found significant associations between such factors, the occurrence of brain lesions and finally schizophrenic symptoms. Although no convincing genetic model had been established to date for schizophrenia, nevertheless it appears that a predisposition not inheritable under the mendelian mode exists and authors showed that disease gets more and more severe over schizophrenic descendants. The risk to be schizophrenic being a first degree relative of the schizophrenic person is about ten time superior than in general population. Indeed, this risk is also about ten time superior in biological parents of schizophrenic adoptees than in biological parents of healthy adoptees. Studies done in monozygotic comparing to dizygotic twins are in favour of an important role played by genetic factors more than socioeducational or psychological factors. Concerning biology, the dopaminergic hypothesis remains shared by numerous authors although direct links with incriminated factors are not well established. Now is suspected the glutamate excitotoxicity with implication of free radicals in schizophrenia. These free radicals are products of various enzymatic activations led by overstimulation of post synaptic receptors (NMDA and AMPA) by the excess glutamate. Therefore, according to that concept, some amino acids as glutamate and derivatives could have through free radicals a noxious effect on neuronal synapses. This could be due to a failing of their recapture at the presynaptic level in addition to a dysfunctioning of the antioxidizing system (glutathion, carnosine, superoxide dismutase, aspartate) to which dopamine and other monoamines might participate. The question is whether or not this theory contributes to shed light on links between: genome, environmental factors and biology in schizophrenia. Through the review and discussion of genetical aspects of schizophrenia, environmental factors and the biological aspect, we intend to revive debate on that question. The articles and authors were selected with regard to the aptness of their publications on that subject, their evolving ideas and finally the interest of their works for neurosciences. This new approach perhaps is opening the way to new therapeutic perspectives in the treatment of schizophrenia based on the antioxidizing substances as shown for some neurological diseases (amyotrophic lateral sclerosis, Parkinson's disease and Huntington's chorea) for which experiments are going on.
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PMID:[Do the glutamate excitotoxicity theory and potential free radicals implication in schizophrenia aetiopathogenesis provide a new enlightenment to links between: genome, environment and biology in the determinism of that disorder?]. 1197 41

Recent data from several reports indicate that free radicals are involved in aetiopathogenesis of many human pathologies including neuropsychiatric disorders such as schizophrenia, bipolar disorder etc. In the present study, we aimed at determining and evaluating levels of malondialdehyde (MDA), a product of lipid peroxidation, and antioxidant enzyme superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity levels in patients diagnosed with schizophrenia (n = 25) and bipolar disorder (n = 23). The control group was composed of 20 healthy subjects. There was a significant increase in MDA levels of patients with schizophrenia and bipolar disorder compared with controls. SOD and GSH-Px activity levels were significantly higher in the schizophrenic group compared with controls. SOD activity levels in bipolar the group were significantly higher than controls whereas there were no significant changes in GSH-Px activity levels in the bipolar group and controls. Significant differences between lipid peroxidation product and antioxidant enzyme (SOD and GSH-Px) activity levels in schizophrenic and bipolar disorder patients compared with controls leads us to believe that these differences are related to the heterogenities in aetiologies of these disorders.
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PMID:Lipid peroxidation and antioxidant enzyme levels in patients with schizophrenia and bipolar disorder. 1197 13

There is great evidence in recent years that oxygen free radicals play an important role in the pathophysiology of schizophrenia. The present study was performed to assess the changes in plasma nitric oxide (NO) and thiobarbituric acid-reactive substances (TBARS) levels, and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and xanthine oxidase (XO) activities in schizophrenic patients compared to age- and sex-matched normal controls. A hundred patients with schizophrenia and 51 healthy volunteers were included in the study. XO, SOD, and GSH-Px activities as well as NO and TBARS levels were estimated by standard biochemical techniques in the plasma of normal healthy controls and schizophrenia patients. In schizophrenia, increased plasma XO activity (P < .0001) and NO levels (P < .0001), decreased SOD activity (P < .0001), and unchanged GSH-Px activity were detected compared to control group. Plasma TBARS levels were increased in schizophrenic patients (P < .01), especially in the residual subtype. TBARS levels in nonsmoker schizophrenic patients were found to be higher than nonsmoker controls. Although TBARS levels in both patients and controls were found to be higher in smokers as compared to nonsmokers, it was not statistically significant. No effects of duration of the illness, gender, and low and high dose of daily neuroleptic treatment equivalent to chlorpromazine on oxidant and antioxidant parameters were observed. Because the dose and the duration of treatment with drugs have no influence on the results, it can be interpreted that the findings are more likely to be related mainly to the underlying disease. These findings indicated a possible role of increased oxidative stress and diminished enzymatic antioxidants, both of which may be relevant to the pathophysiology of schizophrenia. On the other hand, increased NO production by nitric oxide synthetases (NOSs) suggests a possible role of NO in the pathophysiological process of schizophrenia. These findings may also suggest some clues for the new treatment strategies with antioxidants and NO synthase (NOS) inhibitors in schizophrenia.
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PMID:The indices of endogenous oxidative and antioxidative processes in plasma from schizophrenic patients. The possible role of oxidant/antioxidant imbalance. 1236 76

Typical and atypical antipsychotics significantly differ in their neurotransmitter receptor affinity profiles, and their efficacy and side effects in schizophrenic patients. Typical antipsychotics have been found to increase the oxidative (i.e. free radical-mediated) cellular injury in rats. Since schizophrenia also involves oxidative injury, the understanding of differential effects of these antipsychotics on expression of antioxidant enzymes and oxidative injury may be very critical. The effect of chronic exposure of haloperidol (HAL), a typical antipsychotic, was compared to effects of risperidone (RIS) or clozapine (CLZ) or olanzapine (OLZ), atypical antipsychotics on antioxidant defense enzymes and lipid peroxidation in the rat brain. The levels of antioxidant enzymes and hydroxyalkenals (HAEs) were measured in rat brain cytosol and fatty acids were measured in brain cell membranes. Chronic HAL treatment for both 45 and 90 days significantly decreased manganese-superoxide dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD) and catalase (CAT) activity with parallel marked increase in (HAEs), a marker of lipid peroxidation in rat brain. The levels of enzymatic activity very well correlated with the levels of enzyme proteins indicating that the changes were probably in the expression of net protein. However, RIS, CLZ and OLZ treatments did not produce any alterations in the levels of antioxidant enzymes and HAEs, both after 45 and 90 days. There were no alterations in the levels of saturated as well as polyunsaturated fatty acids in brain membranes. These findings indicate that chronic administration of HAL, but none of the studied atypicals induce oxidative stress by persistent changes in the levels of antioxidant enzymes and cause membrane lipid peroxidation.
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PMID:Differential effects of antipsychotics on expression of antioxidant enzymes and membrane lipid peroxidation in rat brain. 1248 69

Repetitive administration of phencyclidine (PCP) in the perinatal period results in cortical apoptosis and a long-lasting deficit in sensorimotor gating. Because these changes are olanzapine-sensitive, we have suggested that the effects of perinatal PCP could be used to model certain aspects of schizophrenia. Studies of PCP and N-methyl-D-aspartate-induced cell death suggested that superoxide could play a role in the pathway leading to death after PCP administration. The purpose of the current study was to determine whether the in vivo administration of M40403, a superoxide dismutase mimetic, could prevent PCP-induced cortical apoptosis and/or deficits in prepulse inhibition. Perinatal rat pups were administered 10 mg/kg PCP on postnatal (PN) days 7, 9, and 11 with or without treatment with 10 mg/kg M40403. Pups were either killed on PN 12 for analysis of various apoptotic markers or they were assessed for prepulse inhibition on PN 24 to 26. Treatment with M40403 2 and 24 h after each PCP treatment prevented PCP-induced increases in two measures of apoptosis in the dorsolateral frontal cortex and in the olfactory cortex. PCP-induced proapoptotic changes in Bax and Bcl-X(L) were also prevented by M40403 treatment. This regimen did not prevent the deficit in prepulse inhibition caused by PCP treatment, but when the treatment regimen was extended through PN 23, M40403 completely prevented the PCP-induced deficit in prepulse inhibition. These data suggest that perinatal PCP treatment leads to long-lasting changes in the pathway(s), leading to cell death and behavioral deficits, and that the superoxide radical plays a critical role in the underlying mechanism.
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PMID:Blockade of phencyclidine-induced cortical apoptosis and deficits in prepulse inhibition by M40403, a superoxide dismutase mimetic. 1249 Jun

cDNA microarrays and two-dimensional gel-electrophoresis in combination with mass spectrometry, were used to screen alterations in mRNA and protein levels, respectively, in cerebral cortex of MK-801-treated rats. The rats were divided in two groups; group 1 (short-term treated) and group 2 (long-term treated). In group 1, four genes were up-regulated and five down-regulated. In group 2, seven genes were up-regulated and six down-regulated. In group 1, the levels of one protein was increased and eight proteins reduced. In group 2, the levels of two proteins were increased and four proteins reduced. Several of the altered genes (casein kinase 2, glutamic acid decarboxylase, synaptotagmin, gamma aminobutyric acid [GABA] transporter, creatine kinase, and cytochrome c oxidase) and proteins (superoxide dismutase, hsp 60, hsp 72 and gamma-enolase) have previously been connected to schizophrenia. Alterations of the genes (microglobulin, c-jun proto-oncogene, 40S ribosomal protein S19, adenosine diphosphate (ADP)-ribosylation factors, platelet-derived growth factor, fructose-bisphophate aldolase A, and myelin proteolipid) and the proteins (stathmin, H+-transp. Adenosine triphosphate (ATP) synthase, pyruvate dehydrogenase, beta-actin and alpha-enolase), have not, to our knowledge, earlier been implicated in schizophrenia pathology. Overall, these results with a combined approach of genomics and proteomics add to the validity of subchronic N-methyl-D-aspartate (NMDA)-receptor antagonist treatment as an animal model of schizophrenia.
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PMID:Comparative genome- and proteome analysis of cerebral cortex from MK-801-treated rats. 1254 8

Blood levels of superoxide dismutase (SOD), measured by radioimmunometric assay, were compared in 68 patients with chronic schizophrenia and 50 normal control subjects. Psychopathology in the patients was assessed with the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Positive Symptoms (SAPS), and the Scale for the Assessment of Negative Symptoms. Blood SOD levels were significantly elevated in schizophrenia compared with control values. SOD levels showed a positive relationship with the BRPS and the SAPS total score in patients.
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PMID:Elevated blood superoxide dismutase in neuroleptic-free schizophrenia: association with positive symptoms. 1258 23

Some reports have shown that schizophrenia is accompanied by the abnormal metabolism of free radicals. The purpose of this study was to investigate the effect of the atypical antipsychotic drug risperidone on blood superoxide dismutase (SOD), a critical enzyme in the detoxification of superoxide radicals, and to explore the relationship between changes in SOD and the therapeutic outcome. Forty-one inpatients with diagnosed schizophrenia (DSM-III-R) were assigned to 12 weeks of treatment with risperidone at a fixed dosage of 6 mg/d after a 2-week washout period. Clinical efficacy was determined with the Positive and Negative Syndrome Scale (PANSS). Blood SOD was assayed by radioimmunoassay (RIA) in schizophrenic patients before and after the 12-week treatment, and the values were compared with those of 50 age-, sex-, and smoking-matched subjects without schizophrenia. Risperidone treatment significantly decreased the initially high blood SOD levels in schizophrenia. There was a significantly positive relationship between the change in SOD at pretreatment and posttreatment and the reduction in the PANSS negative subscore. These findings suggest that risperidone treatment significantly decreased the blood SOD levels of schizophrenic patients, a change which may be associated with the diminishment of symptoms. The limitations of this study are the measurement of SOD levels by RIA rather than biochemical assay; the 2-week washout, which may not be adequate; and the measurement of only SOD enzyme and not the other antioxidant enzymes.
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PMID:The effect of risperidone treatment on superoxide dismutase in schizophrenia. 1264 Feb 13

Transgenic technology, especially the use of homologous recombination to disrupt specific genes to produce knockout mice, has added considerably to the understanding of dopamine (DA) neuron develop, survival and function. The current review summarizes results from knockout mice with the target disruption of genes involved in the development of DA neurons (engrailed 1 and 2, lmx1b, and Nurr1), in maintaining DA neurotransmission (tyrosine hydroxylase, vesicular monoamine transporter, DA transporter, DA D2 and D3 receptors) and important for DA neuron survival (alpha-synuclein, glia cell line-derived neurotrophic factor and superoxide dismutase). As alterations in DA neurotransmission have been implicated in a number of human neuropathologies including Parkinson's disease, schizophrenia and attention deficit/hyperactivity disorder, understanding how specific genes are involved in the function of DA neurons and the compensatory changes that result from loss or reduction in gene expression could provide important insight for the treatment of these diseases.
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PMID:The control of dopamine neuron development, function and survival: insights from transgenic mice and the relevance to human disease. 1267 88


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