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)

Synthetic substance P has been discovered to stimulate significantly the formation of dopa in the limbic, striatum, hemisphere and diencephalon regions of the brain and the lower brain stem. There was no effect upon 5-hydroxytryptophan formation or on tryptophan or tyrosine levels. After inhibition of monoamine synthesis by N'-(DL-SERYL)-N2-(2, 3, 4-trihydroxybenzyl)hydrazine, substance P significantly accelerated the disappearance of dopamine, noradrenaline and 5-hydroxytryptamine. Substance P appears to stimulate monoaminergic neurons in the brain and to serve as an excitatory transmitter in nerve terminals impinging upon dopaminergic cell bodies. A similar stimulation of noradrenaline and 5-hydroxytryptamine indicate a similar transmitter role for noradrenergic and serotonergic neurons. These data strengthen questions about the possible clinical influence of substance P in disease states involving monoaminergic mechanisms including Parkinsonism and schizophrenia.
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PMID:Effect of synthetic substance P on monoaminergic mechanisms in brain. 0 76

The dosage of the whole tryptophan and of the free tryptophan was conducted in 16 normal subjects to establish reference values and in 12 schizophrenic subjects among whom 7 were under treatment and 5 were not. The method of dosage is made by spectrofluorimetry by increasing the native fluorescence of tryptophan. The results give mean values for the free tryptophan and for the ratio of the free tryptophan to the whole tryptophan values that are higher in the schizophrenics than in the normal subjects used as reference, while the whole tryptophan seems to be little modified ; this increase is more noticeable in the schizophrenics under treatment. The limited number of the cases studied does not enable us yet to establish correlations between the increase of the free tryptophan found in some cases and the nature of the schizophrenia, its age and its evolutivity or even the clinical response to the treatment. However, some figures for the free tryptophan being very much higher than the mean value in some schizophrenics, suggest ways of research for understanding the pathogenisis of schizophrenia and the mechanisms of the therapeutic action of the psychotropic drugs.
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PMID:[Study of free and total tryptophan in the plasma. It value in psychiatry]. 0 58

Dopamine and its metabolites homovanillic acid and dihydroxyphenylacetic acid, noradrenaline, serotonin and its metabolite 5-hydroxyindoleacetic acid, and tryptophan and its metabolite kynurenine have been assayed in 9 schizophrenic and 10 control brains, together with the monoamine-related enzymes tyrosine hydroxylase monoamine oxidase, dopamine-beta-hydroxylase, and catechol-o-methyl-transferase. In schizophrenic brains dopamine, noradrenaline and serotonin were significantly increased in some areas of corpus striatum, but there were no significant changes in enzyme activity or monoamine metabolite concentrations in any of the brain areas examined. The findings are not consistent with theories that serotonin or noradrenaline stores are grossly depleted or noradrenaline neurones have degenerated, or that monoamine oxidase activity is abnormal, in schizophrenia, and provide no direct support for the hypothesis that dopamine neurones are overactive.
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PMID:Monoamine mechanisms in chronic schizophrenia: post-mortem neurochemical findings. 4 9

Thirteen cooperative male drug-free chronic schizophrenic patients, and 11 mentally normal male controls were studied. The VER was recorded from scalp leads O1, O2, Oz, C3 and C4 to combined ear reference (A1--A2). The stimulus was an unpatterned flash of single intensity. Compared to normal controls, there were no consistent differences in wave peak latencies or amplitudes for chronic schizophrenics in any brain area tested. When the chronic schizophrenic patients were separated on the basis of high and low tryptophan uptake, using the Frohman--Gottlieb criteria, the high uptake group exhibited normal VERs while in the occipital regions the low tryptophan uptake group exhibited prolonged latencies and an increased amplitude for wave V when compared to normals. From BPRS scores the high tryptophan subgroup indicated a greater degree of psychopathology than the low tryptophan subgroup. The results obtained do not support an indole hallucinogen hypothesis for process schizophrenia.
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PMID:Comparison of the visually evoked response in drug-free chronic schizophrenic patients and normal controls. 8 20

Serotonin (5HT), its chief metabolite 5-hydroxyindoleacetic acid (5 HIAA), its precursor tryptophan, and kynurenine, another metabolite of tryptophan, have been measured in post mortem human brain samples. Concentrations of these metabolites were not found to be significantly different in putamen, hippocampus or temporal cortex from 23 normal subjects compared with 15 subjects in whom a diagnosis of schizophrenia could be restrospectively confirmed. The results have been analysed with respect to cause of death, medication and post mortem changes. Post mortem increases in tryptophan and kynurenine were observed. Some interrelationships between the variables measured within and between the different areas studied are discussed. It is concluded that there is no evidence for a generalised deficit of 5HT in the brain in schizophrenia, nor for gross changes in turnover along the serotonin or kynurenine pathways of tryptophan metabolism in brain.
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PMID:Brain tryptophan metabolism in schizophrenia: a post mortem study of metabolites of the serotonin and kynurenine pathways in schizophrenic and control subjects. 11 Dec 94

The extended theory about a dysfunction of the serotoninergic system in depression and schizophrenia includes the hypothesis of a disturbance in the transport systems of tryptophan and tyrosine from blood to brain. It would be interesting to know if blood cells may be used as a model for the central transport mechanisms of these amino acids. After an oral load, the in vivo distribution of L-tryptophan (50 mg/kg) was studied in the blood plasma, in the different blood cells and its binding to plasma albumin, in six healthy, seven schizophrenic and two depressive subjects. In all the compartments studied, tryptophan reached a peak, 1--2 hours after the load. Before and after the load, the variation of the tryptophan concentration in the erythrocytes was parallel to the plasma free tryptophan, whereas the uptake of this amino acid was higher in leukocytes and thrombocytes than in erythrocytes. However, this model does not show differences between schizophrenic and normal subjects with regard to the transport of tryptophan and tyrosine in these cells.
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PMID:Distribution of tryptophan in erythrocytes, leukocytes and thrombocytes, and its binding to plasma albumin. 29 Jul 55

In order to investigate possible disturbances of the blood-brain transport mechanisms of monoamine precursors in manic-depressive illness and schizophrenia, we have measured the brain arterio-venous difference of DOPA, or 5-HTP, or tyrosine and tryptophan in 36 patients, during the infusion of either L-DOPA or L-5-HTP. The infusion lasted for 30 min, and blood was sampled during and immediately after the infusion, simultaneously in the femoral artery, the jugular vein and a vein of the arm. During the infusion of L-DOPA, manic patients have a higher extraction of L-DOPA than depressive patients and controls. During the infusion of L-5-HTP, pdpressive patients have a higher brain extraction of 5-HTP than manic or schizophrenic patients. In depressive patients, a small uptake of tryptophan correlated with a large outflow of tyrosine was observed. The opposite was seen in manic patients, with an outflow of tryptophan correlated with an uptake of tyrosine. In schizophrenics, there was an outflow of tryptophan and random variations of tyrosine. These brain arterio-venous differences were not correlated with arterio-venous differences for peripheral tissues. Taken together, these results are compatible with a disturbance of the blood-brain transport of amino acids precursors of monoamines in manic-depressive illness and schizophrenia.
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PMID:Blood-brain movements of tryptophan and tyrosine in manic-depressive illness and schizophrenia. 29 Jul 57

It is proposed that the increased dopamine function suggested by the dopamine hypothesis of schizophrenia is a dopaminergic postsynaptic receptor supersensitivity resulting from a dopamine deficiency. In support of this, three double-blind controlled studies conducted on drugs which alter brain dopaminergic activity in a manner different from that of classic neuroleptics are reported. 1) alpha-methyldopa-neuroleptic interaction proved efficacious for schizophrenic positive symptoms but only on a short-term basis. 2) Rubidium improved negative symptoms rapidly, and in contrast has a late onset of action on positive symptoms of schizophrenia. 3) Tryptophan-benserazide was efficacious in controlling both negative and positive symptoms of schizophrenia (although less so than chlorpromazine). It is concluded that currently accepted modes of pharmacological therapy (classical neuroleptics) are in the short-term controlling the dopamine supersensitivity secondary to a deficiency, but contributing in the long-term to increase the dopamine deficiency, and so exacerbate the supersensitivity. More effective forms of treatment may involve the use of agents which alter dopamine activity without inducing dopamine supersensitivity.
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PMID:Evidence of brain dopamine deficiency in schizophrenia. 51 32

The uptake of tryptophan and tyrosine by the brain has been studied in 6 manic-depressive patients and in 8 schizophrenics. In an attempt to saturate the blood-brain transport mechanisms, this uptake has been evaluated by measuring the arteriovenous differences (arterial plasma-internal jugular plasma) of these two amino acids before and after perfusion with L-dopa and L-5-HTP. Considering a positive difference as an uptake and a negative one as an outflow, results show (1) in melancholia an uptake of tryptophan and an outflow of tyrosine; (2) in mania an uptake of tyrosine and an outflow of tryptophan, and (3) in schizophrenia an outflow of tryptophan accompanied with either an uptake or an outflow of tyrosine. In addition, the kinetics of tryptophan binding to plasma proteins and the ratio of tryptophan/tyrosine uptake are different in manic-depressive illness and in schizophrenia. These results support the view that a disturbance in the blood-brain transport mechanisms of tryptophan and tyrosine could be involved in the physiopathology of manic-depressive illness and schizophrenia.
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PMID:[Uptake of tryptophan and tyrosine in some cases of manic depressive psychosis and schizophrenia (author's transl)]. 61 4

Rheumatoid arthritis and schizophrenia have been described in early surveys as mutually exclusive disorders. Such claims are seen as especially interesting in view of: (1) indications that both illnesses often follow prodromes of severe psychological stress, (2) theories regarding hypermethylation of indoleamines producing endogenous psychotogens in schizophrenia, and (3) studies of rheumatoid arthritis reporting excessive binding of L-tryptophan to plasma protein, abnormalities of urinary tryptophan metabolites, decreased serotonin binding capacity of thrombocytes, and decreased MAO activity in joint fluid. Further comparative studies of tryptophan metabolism in schizophrenia and rheumatoid arthritis might enhance knowledge of pathogenesis in either or both diseases.
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PMID:Schizophrenia, rheumatoid arthritis and trytophan metabolism. 65 73


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