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)

Various evidence indicate that schizophrenia is a neurodevelopmental disorder. Epidemiological observations point to oxygen deficiencies during delivery as one of the early risk factors for developing schizophrenia. The aim of the present study was to examine the effect of postnatal anoxia in rats. Anoxia was experimentally induced by placing 9-day-old rat pups for 6 min in a chamber saturated with 100% nitrogen (N(2)). Exposure to anoxia on postnatal day (PND) 9 resulted in significantly reduced subcortical dopamine metabolism and turnover, as measured by striatal 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) concentrations. Furthermore, in the anoxic group only, striatal HVA concentrations were negatively correlated to prefrontal cortical N-acetylaspartate (NAA) levels. Similar findings of distorted prefrontal-subcortical interactions have recently been reported in schizophrenic patients. There was no effect of postnatal anoxia on either baseline or d-amphetamine-induced deficit in the prepulse inhibition (PPI) paradigm in adulthood. Accordingly, although oxygen deficiency early in life has been discussed as vulnerability factor in developing schizophrenia, exposure to postnatal anoxia in the rat does not show clear-cut phenomenological similarities with the disorder.
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PMID:Effects of postnatal anoxia on striatal dopamine metabolism and prepulse inhibition in rats. 1509 22

Deficits of attention are common among individuals with schizophrenia (SZ) and are related both to genetic liability to the disorder and to functional outcome among patients. To explore the brain systems underlying these attentional abnormalities, we compared the response of nine patients with chronic SZ or schizoaffective disorder to that of 10 matched healthy individuals performing a simple visual vigilance task during functional magnetic resonance imaging. The two groups performed equivalently on the task. When the blood oxygen level dependent (BOLD) signal during identification of a target letter among similar-looking letters was compared to the response during fixation trials, both groups showed multiple clusters of significant brain response in widespread cortical regions. Compared with healthy participants, SZ patients showed a diminished response in the inferior frontal cortex and an abnormally enhanced response in right postcentral gyrus, right medial temporal lobe and left cerebellum. The results suggest that abnormalities of functional brain response to attentional tasks can be observed among patients with SZ even when behavioral performance is unimpaired, and provide further evidence that brain systems related to attention are likely to be involved in the pathophysiology of the disorder.
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PMID:Abnormal brain response of chronic schizophrenia patients despite normal performance during a visual vigilance task. 1513 58

Phospholipids located in the cellular membrane play a critical role in the fluid-mosaic model of membrane structure and membrane function. Evidence is mounting for the role of abnormal phospholipid metabolism in some neuropsychiatric disorders including schizophrenia. As an important essential fatty acid (EFA), omega-3 (omega-3) fatty acid series are found in large amounts in fish oil. The aim of this experimental study was to assess the changes of some of the oxidant and antioxidant parameters in the hypothalamus of rats fed with omega-3 EFA diet (0.4 g/kg/day) for 30 days. Eight control rats and nine rats fed with omega-3 were decapitated under ether anesthesia, and hypothalamus was removed immediately. Malondialdehyde (MDA) and nitric oxide (NO) levels as well as superoxide dismutase (SOD) and xanthine oxidase (XO) enzyme activities in the hypothalamus were measured. SOD activity was significantly decreased in omega-3 EFA treated group compared to control group (p < 0.014). Tissue MDA and NO levels were also decreased in omega-3 EFA treated group compared to control rats (p < 0.0001). Xanthine oxidase activity was found to be increased in omega-3 EFA treated rats when compared to the control group (p < 0.0001). Taken together, this preliminary animal study provides strong support for a therapeutic effect of omega-3 EFA in some neuropsychiatric disorders in which reactive oxygen species (ROS) are recently accused to be an important physiopathogenetic factor.
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PMID:Hypothalamic superoxide dismutase, xanthine oxidase, nitric oxide, and malondialdehyde in rats fed with fish omega-3 fatty acids. 1527 95

The dominant research subject on schizophrenia, mood disorders, autism and other central nervous system diseases has been related to neurotransmitter system abnormalities. For example, the dopamine hypothesis states that schizophrenia is the result of dopaminergic hyperactivity. The therapeutic approach has also been directed towards finding agents which will modulate or regulate these neurotransmitter systems at any step. There is substantial and mounting evidence that subtle abnormalities of reactive oxygen species (ROS) and nitric oxide (NO) may underlie a wide range of neuropsychiatric disorders. NO has chemical properties that make it uniquely suitable as an intracellular and intercellular messenger. It is produced by the activity of nitric oxide synthases which are present in peripheral tissues and in neurons. On the other hand, NO is known to be an oxygen radical in the central and peripheral nervous systems. NO has been implicated in a number of physiological functions such as noradrenaline and dopamine releases, memory and learning and certain pathologies such as schizophrenia, bipolar disorder and major depression. Evidence has been considered here for the proposal that an abnormality of NO metabolism may be a contributory factor in some neuropsychiatric disorders. The direct evidence for NO abnormalities in schizophrenia and other psychiatric disorders remains relatively limited to date, although there are some clinical and experimental studies. The suggestion that NO and other ROS may play a role in some neuropsychiatric disorders clearly has important implications for new treatment possibilities. The primary objective of the present review was to summarize and critically evaluate the current knowledge regarding a potential contribution of NO to the neuropathophysiology of schizophrenia as well as other neuropsychiatric disorders.
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PMID:Nitric oxide as a physiopathological factor in neuropsychiatric disorders. 1534 Nov 94

Reactive oxygen species (ROS) have been suggested to play an important role in physiopathology of schizophrenia. The major intracellular antioxidant enzymes, copper-zinc superoxide dismutase in the cytoplasm and manganese superoxide dismutase (Mn-SOD) in the mitochondria, rapidly and specifically reduce superoxide radicals to hydrogen peroxide. Polymorphisms in the genes encoding antioxidant enzymes should therefore result in predisposition to schizophrenia. The present study was performed to assess whether there is a genetic association between a functional polymorphism (Ala-9Val) in the human Mn-SOD gene in schizophrenic patients (n=153) and healthy controls (n=196) using a PCR/RFLP method. Significant differences in the genotypic distribution between schizophrenics and controls were observed. Genotypic distribution with 14 (9.2%) Ala/Ala, 106 (69.3%) Ala/Val and 33 (21.6%) Val/Val subjects in schizophrenia was different from those of controls with 46 (23.5%), 83 (42.3%) and 67 (34.2%), respectively (p<0.0001). When the patients with schizophrenia were divided into the subgroups as disorganized, paranoid and residual, there was a significant difference in genotypic distribution among the subgroups (chi2=11.35, df=4, p=0.023). This association between -9Ala Mn-SOD allele and schizophrenia suggests that -9Ala variant may have a contribution in the physiopathogenesis of schizophrenia. Further investigations are warranted in larger populations with other susceptible genes that might be associated with schizophrenia.
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PMID:Association between Ala-9Val polymorphism of Mn-SOD gene and schizophrenia. 1657 66

Blood oxygen level dependent (BOLD) signals characteristically exhibit an overshoot (transient signal increase) at the beginning of fMRI task blocks. This onset transient has often been overlooked as an independent measure of neuronal activity, but it may represent unique functional processes. We examined onset transient responses in normal subjects and individuals with schizophrenia performing three cognitive tasks. These analyses revealed a regionally specific and task specific attenuation of the onset transient in individuals with schizophrenia during performance of a working memory task. Furthermore, this attenuation was often not accompanied by a corresponding population difference in the sustained response, and is missed through conventional fMRI analysis techniques. Relevance of these findings to both an interpretation of the onset transient and the pathology of schizophrenia are discussed.
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PMID:The BOLD onset transient: identification of novel functional differences in schizophrenia. 1580 78

Several authors have suggested that psychological stress induces the production of reactive oxygen species (ROS). Several studies have supported the idea that bilirubin exerts antioxidative effects in vivo, and it was reported psychological stress provokes bilirubin oxidation in vivo [Yamaguchi T., Shioji I., Sugimoto A., Yamaoka M., 2002. Psychological stress increases bilirubin metabolites in human urine. Biochem. and Biophys. Res. Commun. 293, 517-520]. We investigated whether the concentration of bilirubin oxidative metabolites (biopyrrins) is increased in urine from patients with psychiatric disorders. The concentration of biopyrrins in urine of 25 patients with psychiatric disorders (schizophrenia, 15; depression, 10) was compared with 96 healthy volunteers. The concentrations of biopyrrins, as measured by enzyme-linked immunosorbent assay, were normalized to the urinary concentration of creatinine. The concentration of biopyrrins in patients with psychiatric disorders (schizophrenia and depression) was significantly higher than that of healthy volunteers. In schizophrenia, biopyrrins levels correlated with scores of the Brief Psychiatric Rating Scale (BPRS), and in depression, biopyrrins levels correlated with scores of the Hamilton Depression Rating Scale (HAM-D). These finding suggest that psychotic states are associated with an increase in the oxidative metabolites of bilirubin in human urine.
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PMID:Urinary excretion of biopyrrins, oxidative metabolites of bilirubin, increases in patients with psychiatric disorders. 1582 Apr 12

We previously found that the atypical antipsychotic drugs (APDs) clozapine, olanzapine, quetiapine, and risperidone reduce PC12 cell death induced by hydrogen peroxide, N-methyl-4-phenylpyridinium ion, or beta-amyloid peptide (Abeta(25-35)). Such neurotoxic substances have in common the capability of causing oxidative stress. Atypical APDs have been used in treating schizophrenia and in treating psychotic symptoms of patients with Alzheimer's disease (AD), in which Abeta is involved by causing oxidative stress. Therefore, we hypothesized that atypical APDs might alleviate oxidative stress in PC12 cells, thus protecting them from apoptosis. PC12 cells were seeded in plates or chambers for 24 hr and cultured for another 24 hr with olanzapine or quetiapine in the medium, and then the cells were cultured in the new medium containing Abeta(25-35) and/or olanzapine, quetiapine, but not serum, for various periods. It was shown that cultures treated with olanzapine + Abeta(25-35), or quetiapine + Abeta(25-35), had significantly higher cell viabilities and lower rates of apoptosis compared with the cultures exposed only to Abeta(25-35). In addition, the drugs blocked the activation of caspase-3 caused by Abeta(25-35). Furthermore, olanzapine and quetiapine prevented Abeta(25-35)-induced overproduction of intracellular reactive oxygen species, Abeta(25-35)-induced decrease in mitochondrial membrane potential, and Abeta(25-35)-induced changes in activities of the key antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase. In consideration of the wealth of evidence linking oxidative stress to the pathophysiology of schizophrenia and AD, these findings give us a new insight into the therapeutic actions of atypical antipsychotics in patients with the disorders.
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PMID:Olanzapine and quetiapine protect PC12 cells from beta-amyloid peptide(25-35)-induced oxidative stress and the ensuing apoptosis. 1594 79

A possible role for oxidative stress in the pathophysiology of tardive dyskinesia (TD) has previously been proposed (reviewed in Andreassen and Jorgensen [O.A. Andreassen, H.A. Jorgensen, Neurotoxicity associated with neuroleptic-induced oral dyskinesias in rats Implications for tardive dyskinesia? Prog. Neurobiol. 61 (2000) 525-541]). Long-term administration of antipsychotics alters dopaminergic turnover, which results in increased formation of reactive oxygen species (ROS). This is hypothesized to lead to TD through neuronal toxicity as a consequence of oxidative stress. In the present study, the relationship between TD and a functional polymorphism of the gene coding for human glutathione S-transferase P1 (GSTP1), an important antioxidant enzyme involved in the detoxification of ROS, was studied in 225 chronic treatment-refractory patients with schizophrenia. An isoleucine (Ile) to valine (Val) substitution at codon 105 (Ile105Val) in the GSTP1 gene was genotyped. No significant difference in total AIMS scores was found among patients in the three genotype groups (chi(2)=1.47, d.f.=2, p=0.48). Moreover, no significant differences in genotype (chi(2)=0.05, d.f.=2, p=0.98) or allele frequencies (chi(2)=0.00, d.f.=1, p=1.00) were observed between subjects with and without TD. Our results suggest that the GSTP1 gene polymorphism does not confer increased susceptibility to TD, although further studies are warranted before a conclusion can be drawn.
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PMID:Association study between a functional glutathione S-transferase (GSTP1) gene polymorphism (Ile105Val) and tardive dyskinesia. 1603 55

Dopamine receptor activation is thought to contribute adversely to several neuropathological disorders, including Parkinson's disease and schizophrenia. In addition, dopamine may have a neuroprotective role: dopamine receptor agonists are reported to protect nerve cells by virtue of their antioxidant properties as well as by receptor-mediated mechanisms. White matter injury can also be a significant factor in neurological disorders. Using real-time RT-PCR, we show that differentiated rat cortical oligodendrocytes express dopamine D2 receptor and D3 receptor mRNA. Oligodendrocytes were vulnerable to oxidative glutamate toxicity and to oxygen/glucose deprivation injury. Agonists for dopamine D2 and D3 receptors provided significant protection of oligodendrocytes against these two forms of injury, and the protective effect was diminished by D2 and D3 antagonists. Levels of oligodendrocyte D2 receptor and D3 receptor protein, as measured by Western blotting, appeared to increase following combined oxygen and glucose deprivation. Our results suggest that dopamine D2 and D3 receptor activation may play an important role in oligodendrocyte protection against oxidative glutamate toxicity and oxygen-glucose deprivation injury.
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PMID:Dopamine D2 and D3 receptor agonists limit oligodendrocyte injury caused by glutamate oxidative stress and oxygen/glucose deprivation. 1607 34


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