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)

Catechol O-methyltransferase of lysed human red blood cells was assayed under optimal conditions, using saturating concentrations of the substrates, S-adenosyl-L-methionine and 3-4-dihydroxybenzoic acid. The mean enzyme activity found in 24 normal subjects was 29-2 nmol/hr/ml RBC. The mean activity in blood of 33 female unipolar depressives was not significantly different from normal. However, higher enzyme activities were observed in the blood of 11 schizophrenic patients (38-9 nmol/hr/ml RBC). Partially purified enzyme preparations from blood of normal and schizophrenic individuals were indistinguishable with respect to substrate specificities, isoelectric pH values, and ratios of the two O-methylated products. Therefore it is unlikely that any defect in O-methylation which may occur in schizophrenia can be attributed to a change in the intrinsic properties of erythrocyte catechol O-methyltransferase.
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PMID:Catechol O-methyltransferase in red blood cells of schizophrenic, depressed, and normal human subjects. 0 50

The transmethylation hypothesis of schizophrenia was reviewed with considerations that large doses of methionine when combined with a monoamine oxidase inhibitor lead to exacerbation of psychotic symptoms in a significant percentage of chronic schizophrenic patients. It was noted that nicotinic acid in the dosage of 3,000 mg/day can neither prevent nor counteract the psychopathology thus induced.
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PMID:Transmethylation hypothesis of schizophrenia: methionine and nicotinic acid. 33 34

L-Methionine had no behavioral effects in normal humans and failed to increase concentrations of S-adenosylmethionine (methyl donor) in human or rat blood, while increasing rat liver levels more than fivefold. Methionine or S-adenosylmethionine in very high doses had almost no effect on methylation of tritiated levodopa in rodent tissues; various "methyl acceptor" molecules, including nicotinamide, guanidineacetic acid, and estradiol similarly had little effect. In rabbit lung, methionine and S-adenosylmethionine not only failed to increase production of dimethyltryptamine, but actually decreased it, possibly due to end-product inhibition by S-adenosylhomocysteine, which also strongly inhibited methylation of dopa in rat. These results fail to support several predictions of the "methylation hypothesis" concerning the pathophysiology and potential treatment of idiopathic psychotic disorders and leave the consistent clinical worsening effects of methionine in schizophrenia unexplained.
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PMID:Methylation hypothesis. 42 May 48

Beta-Leu5-endorphin, a relative of "normal" beta-endorphin in which leucine is substituted for methionine at position 5 of the latter, has previously been found in high concentrations in the dialysate of schizophrenics. Its removal from plasma by means of hemodialysis has been claimed to relive the symptoms of schizophrenia. Using a highly sensitive radioimmunoassay of equal sensitivity to beta-endorphin and beta-leu5-endorphin, we have compared the plasma immunoreactivity of three schizophrenic patients befofe and after performance of their first session of membrane hemoperfusion. As compared to normal subjects, plasma beta-endorphin-like immunoreactivity was not greatly elevated in the schizophrenic patients before hemoperfusion.However, instead of the expected decrease, a consistent increase in the plasma levels of immunoreactive beta-endorphin was detected after hemoperfusion. In vitro experiments in which two different membranes and hemodialysis as well as hemoperfusion were used, revealed that synthetic beta-leu5-endorphin (and beta-endorphin) from human plasma was not cleared with any of these methods. This finding is inconsistent with the hypothesis that the claimed therapeutic effects of hemodialysis in schizophrenics are due to the removal of a beta-endorphin-like material from the plasma. Consequently, it seems to be unprobable that high concentrations of beta-leu5-endorphin occur in the dialysate or ultrafiltrate of schizophrenics.
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PMID:Endorphins in schizophrenia: hemodialysis/hemoperfusion are ineffective in clearing beta-Leu5-endorphin and beta-endorphin from human plasma. 53 84

Previous work has indicated that abnormal methylation processes may be associated with schizophrenia. In this study, leukocytes from patients with schizophrenia were incubated with methyl-14C-L-methionine and the evolved 14CO2 measured. With increasing concentration of methionine, the evolved 14CO2 was lower in the patients than in normal control subjects. The incorporation of 14C into protein was the same in both groups, and when carboxyl-14C-L-methionine was used the evolved 14CO2 was the same in both groups, thus excluding the possibility that altered incorporation into protein or oxidation of the methionine molecule as a whole were responsible. The observed differences in methionine-methyl metabolism suggest that an abnormality in transmethylation processes or in oxidation of the methyl group to CO2 is associated with schizophrenia. That this occurs in a peripheral tissue indicates that the abnormality is not restricted to the central nervous system.
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PMID:Altered metabolism of the methionine methyl group in the leukocytes of patients with schizophrenia. 73 53

The original transmethylation hypothesis of schizophrenia has evolved with time and experiment to the present concept that a defect in the methyl-carbon metabolic pathway may be causative in this illness. Various researchers have proposed that specific steps in the methyl-carbon pathway may be defective, and have presented evidence to support these possibilities. We have tested the general concept of the hypothesis by administering methionine labeled with 11C or 14C in the S-methyl carbon to patients with schizophrenia and to controls and measured the expiration of 11CO2 and 14CO2. We found that the rate and total expiration of labeled CO2 were three times less in the patients than in the controls, with no overlap of data points in the two groups. Specific steps in the methylcarbon pathway that might be defective and produce the results seen here are discussed in light of this and other researchers' findings.
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PMID:Tracer kinetic evidence for abnormal methyl metabolism in schizophrenia. 147 88

The effect of methionine on cerebral content of dopamine, serotonin and major acidic metabolites was studied in distinct CDF-1 mouse brain regions. Methionine was administered 30 mg/kg for five trials over 24 h and mice were sacrificed 30 min post the terminal treatment. Methionine exerted differential effects on regional brain concentrations of 3,4-dihydroxyphenylacetic acid and serotonin. The results suggest methionine-mediated decreases of dopamine turnover in the hippocampus and medulla compared to increases of serotonin turnover in the cerebral cortex and midbrain regions. The results indicate a central action for methionine as related to endogenous neurotransmitters measured which may precede the abnormal O- or N-dimethylation ascribed to methionine and the insuing adverse effects postulated in schizophrenia.
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PMID:Effect of methionine on regional CDF-1 mouse brain monoamines. 227 63

Compared to healthy controls, unmedicated schizophrenic patients had significantly higher plasma concentrations of taurine, methionine, valine, isoleucine, leucine, phenylalanine, and lysine. Except for taurine, these amino acids share the L-transport system for neutral amino acids. In the patients, homovanillic (HVA) acid levels in CSF were decreased and the plasma levels of the amino acids competing with tyrosine and tryptophan for transport into the brain, were all negatively correlated to the CSF concentrations of HVA and 5-HIAA. These findings could be explained by a change in the affinity of the L-system or by a decrease in its overall capacity in schizophrenia. Raised plasma levels of the competing amino acids may limit the brain uptake of tyrosine, leading to a diminished dopamine turnover, and resulting in a compensatory development of supersensitive dopamine receptors.
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PMID:Plasma amino acids in relation to cerebrospinal fluid monoamine metabolites in schizophrenic patients and healthy controls. 241 98

Dopamine has been accepted as a possible etiological factor in schizophrenia and most studies have demonstrated that the ingestion of methionine by schizophrenics exacerbated their psychosis. Unfortunately, the methylation theory has failed to support the dopamine theory in schizophrenia. This paper will attempt to demonstrate why abnormal histamine metabolism in schizophrenia can explain the effect of methionine in worsening schizophrenia in certain patients.
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PMID:Histamine methylation in schizophrenia. 268 45

In a double blind, cross-over study 10 chronic schizophrenic patients with productive symptoms in spite of neuroleptic treatment received the methionine-enkephalin analogue FK 33-824 2 mg i.m. daily for 7 consecutive days. Ratings performed by the Brief Psychiatric Rating Scale did not show any significant differences between FK 33-824 and the active placebo pentobarbital. The clinical condition of one patient worsened during and after the administration of FK 33-824. It is suggested that this might be due to a dopamine stimulating effect. The discrepancy between the findings of the present and a previous open study is discussed. The present study does not support the hypothesis of dysfunction of the endorphin system in schizophrenia.
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PMID:Enkephalin analogue in schizophrenia. Double blind cross-over trial. 351 52


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