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)

We examined the activity of phospholipase A2 in Epstein-Barr virus-transformed lymphoblast cell lines established from ten schizophrenic patients and ten controls. A novel method for determination of enzyme activity in whole cells was employed, by measuring the hydrolysis of a fluorescent analogue of phosphatidylcholine. No significant difference in phospholipase A2 activity was found between the groups. These results suggest that the previously reported changes in phospholipase A2 activity in plasma and in fresh peripheral cells are indicative of environmental influences and not of "trait" characteristics intrinsic to schizophrenia.
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PMID:Phospholipase A2 activity in Epstein-Barr virus-transformed lymphoblast cells from schizophrenic patients. 173 85

The intracellular enzyme phospholipase A2 (PLA2) plays an essential role in the breakdown of membrane phospholipids, which regulate the physicochemical properties of the cell membrane. In the brain PLA2 has been reported to influence receptor function and signal transduction. Regarding dopaminergic neurons, data from animals experiments and from binding studies suggest that PLA2 activation reduces dopaminergic neurotransmission. In the present study we investigated intracellular PLA2 in platelets from 31 DSM-III-R paranoid schizophrenic patients (15 neuroleptic-naive) compared to 31 healthy individuals and to 31 non-schizophrenic psychiatric controls, both matched to the schizophrenics by age and sex. Platelet PLA2 activity was significantly increased in schizophrenics as compared to healthy and to psychiatric controls. Neuroleptic treatment reduced significantly the enzyme activity. Our findings in platelets suggest an accelerated breakdown of membrane phospholipids in schizophrenia. An accelerated phospholipid breakdown has also been reported in the frontal cortex from schizophrenic patients. Further studies should clarify whether increased PLA2 in the brain, as observed in platelets, could contribute to a frontal dysfunction in schizophrenia.
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PMID:Increased platelet phospholipase A2 activity in schizophrenia. 754 40

The objective of the present work was to evaluate on the basis of the authors' data and data in the literature the role of phospholipase A2 in the pathogenesis of schizophrenia. The authors submit available literature pertaining to the problem as well as their own experimental findings. Based on the submitted facts, it cannot be states that phospholipase A2 is a specific marker of schizophrenia.
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PMID:[Phospholipase A2 in schizophrenia]. 862 10

The fatty acids of cell membrane phospholipids are essential for normal membrane structures, for the functioning of membrane-bound and membrane-associated proteins and for normal cell-signalling responses. In dyslexia, there is evidence for reduced incorporation of docosahexaenoic acid and arachidonic acid into cell membranes, while in schizophrenia, there is evidence for an increased rate of docosahexaenoic acid and arachidonic acid loss from membranes because of enhanced phospholipase A2 activity. The presence of both defects will cause a much greater degree of abnormality than either one alone. It is hypothesized that unequivocal clinical schizophrenia may occur when both genes are present in the same individual. The dyslexia gene along will produce dyslexia while the schizophrenia gene alone may produce bipolar or schizoaffective disorders. These proposals could explain: 1. The reduced asymmetry of the brain, especially of the planum temporale in both schizophrenia and dyslexia; 2. The schizotypal personality characteristics of dyslexics; 3. The increased risks of dyslexia in families with a schizophrenic proband; 4. The increased risks of bipolar and schizoaffective disorders in families with a schizophrenic proband; 5. The earlier onset and possibly increased severity of both disorders in males since females have a lower requirement for arachidonic acid and docosahexaenoic acid; 6. The absence of selective pressure against schizophrenia since reproduction would be impaired only when the schizophrenic gene coexisted with a dyslexic gene. The schizophrenic gene alone might even lead to improved reproductive performance.
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PMID:Possible relevance of phospholipid abnormalities and genetic interactions in psychiatric disorders: the relationship between dyslexia and schizophrenia. 877 Oct 57

Clinical, biochemical and genetic evidence now indicates that schizophrenia is a disorder of membrane phospholipid metabolism associated with increased loss of highly polyunsaturated fatty acids from membranes owing to enhanced activity of a phospholipase A2. This changes the properties of membranes throughout the body and is responsible for such physical abnormalities as reduced vasodilator responses to niacin and histamine and altered immunological functions. A modest membrane abnormality is likely to produce its most serious consequences in the brain, which requires the co-ordinated sequential and parallel activities of millions of neurons. The concept leads to testable proposals for relatively simple and safe treatment modalities.
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PMID:Schizophrenia as a membrane lipid disorder which is expressed throughout the body. 888 16

Biochemical studies have shown that a proportion of schizophrenics have an abnormal fatty acid composition in their red blood-cell membrane phospholipids and it has been suggested that this might be due to altered levels of the enzyme phospholipase A2 (PLA2). A recent report indicated that there was an association between schizophrenia and alleles of a poly-A repeat polymorphism close to the 5' end of the PLA2 gene. We report the analysis of this polymorphism in a series of 58 schizophrenic patients and 56 controls and find no evidence for allelic association.
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PMID:Lack of association between schizophrenia and a polymorphism close to the cytosolic phospholipase A2 gene. 932 23

We recently reported that the activity of a calcium-independent subtype of phospholipase A2 is increased in blood of patients with schizophrenia. The present investigation examined whether similar changes take place in brain of patients with this disorder, and for comparison, in patients with bipolar disorder. The activity of two classes of PLA2, calcium-stimulated and independent, were assayed in autopsied temporal, prefrontal and occipital cortices, putamen, hippocampus and thalamus of 10 patients with schizophrenia, 8 patients with bipolar disorder and 12 matched control subjects. Calcium-independent PLA2 activity was increased by 45% in the temporal cortex of patients with schizophrenia as compared with the controls but was not significantly altered in other brain areas. In contrast, calcium-stimulated PLA2 activity was decreased by 27-42% in the temporal and prefrontal cortices and putamen, with no significant alterations in other brain regions. Brain PLA2 activity was normal in patients with bipolar disorder. Calcium-stimulated PLA2 activity was normal in cortex, cerebellum and striatum of rats treated acutely or chronically with haloperidol, whereas calcium-independent PLA2 activity was decreased in striatum of chronically treated animals, indicating that altered PLA2 activity in patients with schizophrenia is unlikely to be a direct effect of medication. Studies of the cellular role played by PLA2 suggest that decreased calcium-stimulated PLA2 activity, as also occurs in striatum of chronic human cocaine users, may be due, in part, to increased dopaminergic activity in the disorder, whereas increased calcium-independent PLA2 activity may be related to abnormal fatty acid metabolism and oxidative stress in schizophrenia.
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PMID:Differential alteration of phospholipase A2 activities in brain of patients with schizophrenia. 1006 28

The S100 proteins are a family of calcium-binding proteins found in the central and peripheral nervous systems of vertebrates. S100beta, the most abundant member of this family in the CNS, mediates calcium signal transduction, and shows neurotrophic, gliotrophic and mitogenic actions that influence the development and maintenance of the nervous system. Another member of the S100 family (S100A10) was found to modulate phospholipid turnover by inhibiting the activity of enzyme phospholipase A2 (PLA2). We determined the concentration of S100beta protein in the plasma of 23 medicated schizophrenic patients and 23 healthy controls. S100beta protein accounts for 96% of the total S100 in the brain. Schizophrenic patients showed reduced S100beta concentrations (p=0.003), and this finding was not related to clinical variables or to intake of antipsychotic medication. Decreased S100beta could be related to the findings of increased PLA2 activity and to brain maldevelopment in schizophrenia. These results are discussed further with respect to the role of adenosine in S100beta release.
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PMID:Decreased S100-beta protein in schizophrenia: preliminary evidence. 1085 27

During the last few years analyses of the lipidmetabolism have been performed on schizophrenic patients. Anabolic and katabolic metabolite-concentrations from blood and cell samples have been measured. By means of new investigation techniques, such as 31P-magnetic-resonance-spectroscopy, it is nowadays even possible to determine membrane metabolites non-invasively in vivo. Arachidonic acid deficits in peripheral cell membranes, turnover of phosphodiesters in the brain, increased phospholipase A2 (PLA2)-activity in serum and blood cells, disturbed niacin-response and abnormalities of the PLA2-gene are summarised as phospholipid-membrane-hypothesis of schizophrenia. Although there is some evidence for correlations between those findings and psychotic symptoms, the connection to the pathogenesis of schizophrenia still has speculative character. Furthermore it has to be confirmed that peripheral biochemical findings acquired in schizophrenics are transferable to the metabolism of the central nervous system. Actual results of enzyme and metabolite measurements reported in literature and current findings of our own 31P-MR-spectroscopic studies are surveyed and summarised. To point out possible connections between the phospholipid-metabolism of the central nervous system and of peripheral blood-cells, systemic approaches are considered.
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PMID:[Diseases of phospholipid metabolism as possible pathogenetic factors in schizophrenia. Current findings and critical evaluation]. 1094 56

Research findings are increasingly reporting evidence of physiological abnormalities in dyslexia and sites for dyslexia have been identified on three chromosomes. It has been suggested that genetic inheritance may cause phospholipid abnormalities in dyslexia somewhat similar to those found in schizophrenia. A key enzyme in phospholipid metabolism, Type IV, or cytosolic, phospholipase A2 (cPLA2), releases arachidonic acid (AA), a 20-carbon fatty acid, which is the major source of production of prostaglandins and leukotrienes. An entirely new assay, which for the first time has enabled determination of the amount of the enzyme rather than its activity, was used to measure cPLA2 in dyslexic-type adults and controls and the two groups were found to differ significantly, the dyslexic-types having more of the enzyme. A report elsewhere of schizophrenics having even greater amounts of the enzyme suggests that dyslexia may be on a continuum with schizophrenia, as may be other neurodevelopmental disorders - which have also been described as phospholipid spectrum disorders.
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PMID:Increased levels of cytosolic phospholipase A2 in dyslexics. 1097 Jul 11


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