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

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

In order to study the correlations between the metabolism of biogenic monoamines and the type of development) of schizophrenia, the morning urine excretion of 30 patients (15 with continuous progressive schizophrenia and 15 with shift-like forms of development) was examined. The author studied the percentage of distribution of data, dophamine, noradrenaline and adrenaline and the correlation between these ingredients in the catecholamine system, as well as the distribution of tryptophane. It was established that in schizophrenia there is a noradrenaline deficit and a drop in the activity of tryptophane metabolism towards the serotonin way. Besides, in patients with continuous progressive forms of the disease there was a simultaneous drop in the intensity of dophamine synthesis from dopha, while in patients with shift-like schizophrenia-an excess of dophamine, conditioned probably not only by an inhibition of phamine-B-oxydase, but by an increase of dophadecarboxylase activity.
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PMID:[Excretion of catecholamines and tryptophan derivatives in schizophrenia]. 13 32

Dopamine, noradrenaline, glutamate decarboxylase (GAD) and choline acetyl-transferase (CAT) were measured in post-mortem brain samples from more than 50 patients dying with a hospital diagnosis of schizophrenia and an equal number of controls. GAD was measured in 14 different brain regions, and was significantly lower in both control and schizophrenia patients who died following a protracted illness. If GAD values from patients who died suddenly were compared, no significant differences were observed between the control and schizophrenia groups. There was also no differences between the CAT values measured in 13 different brain regions in the two groups. Noradrenaline values were not different in the two groups in most limbic areas or in the caudate nucleus, but were elevated in the schizophrenic group in nucleus accumbens and in anterior perforated substance. These differences were not, however, statistically significant. On the other hand dopamine concentrations in nucleus accumbens and in anterior perforated substance were significantly elevated (by 34 and 95 per cent, respectively) in the schizophrenia group as compared with controls, although dopamine values were not different in caudate nucleus, putamen, septal nuclei or amygdala. The finding of elevated concentrations of dopamine in certain areas of the limbic forebrain in schizophrenia is discussed in relation to current hypotheses of the involvement of dopamine in this illness, and the difficulties of determining whether the observed changes are related to chronic treatment with antischizophrenic drugs.
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PMID:Increased dopamine concentration in limbic areas of brain from patients dying with schizophrenia. 45 44

The brains from 12 schizophrenic patients were investigated post-mortem for their content of noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT), homovanillic acid (HVA), and 5-hydroxyindolacetic acid (5-HIAA). Six of the schizophrenics had been lobotomized 25--30 years prior to death. A control group matched for age was collected in the autopsy room. The concentrations of NA, DA, and HVA in different parts of the brain from the schizophrenic group did not differ from those of the controls. 5-HT was determined in 11 nuclei or areas of the brain. The schizophrenic group had lower mean values compared with the controls, and in the hypothalamus, medulla oblongata, and hippocampus the difference was at a significant level. 5-HIAA was determined in six areas of the brain but only in a few cases. There was a trend towards lower means of 5-HIAA in the schizophrenics. Cause of death, medication, food intake, age, time between death and autopsy, time the corpses have lain in room temperature, and dissection technique are discussed in relation to these findings. These variables have to be kept under careful control before changes can be claimed as having pathogenetic importance for schizophrenia or for the progressing dementia in this disease.
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PMID:Monoamines and monoamine metabolites in brains from demented schizophrenics. 47 74

Chronic administration of amphetamine to cats (twice daily, in doses increasing from 5 to 15 mg/kg over a 10-day period) elicited a number of behaviors, e.g., limb flick and abortive groom, characteristic of the action of hallucinogenic drugs and dependent on a depression of central serotonergic neurotransmission. This drug treatment produced large decreases (-40 to -60%) in central nervous system serotonin (5-HT) and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA), when measured either 6 or 24 hr after the last amphetamine injection. The rate of limb flicking returned to a predrug level approximately 5 days after drug withdrawal, at which time 5-HT and 5-HIAA levels had returned to within 30 to 40% of base line. Both 5-HT and 5-HIAA returned to base-line levels within 14 days after drug withdrawal. Norepinephrine (NE), dopamine (DA) and DA metabolites were decreased 60 to 95% by chronic amphetamine treatment and showed little recovery within the 14 days after drug withdrawal. A second experiment examined the latency to onset of the behavioral and neurochemical changes with a constant dose of amphetamine (7.5 mg/kg, twice daily). Limb flicking was significantly increased above base-line levels following 3 days of amphetamine administration, at which time 5-HT and 5-HIAA levels were decreased 30 to 40%. NE, DA and DA metabolites were decreased approximately 50 to 90% by this treatment regimen. A third experiment examined the effects of a low dose of amphetamine (3.75 mg/kg), injected more frequently (every 6 hr for 6 days), to approximate the administration pattern in human amphetamine abuse. This treatment produced significant increases in limb flicking and abortive grooming on days 5 and 6 and resulted in 30 to 40% depletions of 5-HT and 5-HIAA. NE, DA and DA metabolites were decreased by approximately 50 to 90%. These data are discussed in relation to a role for serotonin in amphetamine psychosis and schizophrenia.
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PMID:Chronic amphetamine administration to cats: behavioral and neurochemical evidence for decreased central serotonergic function. 50 68

On the basis of post-mortem studies it has been proposed that the central deficit in schizophrenia may be in noradrenergic transmission. It has also been proposed that there is a substantial central contribution to the excretion of the noradrenaline metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) and more particularly of its sulphate conjugate in man. There is throught to be a lesser central contribution to the excretion of the other major noradrenaline metabolites, vanillylmandelic acid (VMA) and the glucuronide conjugate of MHPG. A strong negative correlation was found between severity of illness in a group of 18 unmedicated chronic schizophrenic patients and their 24-h excretion of MHPG-sulphate but not of MHPG-glucuronide or VMA. However there was no significant difference in the mean excretion of MHPG conjugates or of VMA between the schizophrenic group and an institutional control group. This supports the idea of a relation between MHPG-sulphate excretion and central noradrenergic activity, but suggests that reduced brain noradrenaline turnover is neither necessary nor sufficient for schizophrenia to occur. One possible explanation is that reduced turnover pre-disposes towards a more severe illness in schizophrenics.
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PMID:Determination of 3-methoxy-4-hydroxyphenylglycol conjugates in urine. Application to the study of central noradrenaline metabolism in unmedicated chronic schizophrenic patients. 82 75

After administration of isadrine excretion of noradrenaline was increased in schizophrenic patients with symptoms of depression or anxiety. This phenomenon was not observed in healthy persons and in patients with circular depression. Data on liberation of noradrenaline by other amines in schizophrenia and displacement of noradrenaline in schizophrenia by isadrine, which does not accumulate in normal storage sites, suggest that storage of noradrenaline is impaired in schizophrenia.
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PMID:[Catecholamine storage in schizophrenia]. 91 79

Three main biogenic amine hypotheses for the origin of schizophrenia are discussed. The dopamine theory of schizophrenia postulates a pathogenetic connection between the disease and changes in the activity of dopaminergic cells in the brain. The theory is mainly based on findings on the mechanism of action of neuroleptics, on the clinical features and pharmacology of the amphetamine psychosis, and on some amphetamine effects in animals. Several results are in good agreement with the assumption of a state of hyperactivity of central dopamine neurons, whereas others, e.g. the lack of an increased dopamine turnover, are not. According to another theory, schizophrenia is caused by reversible damage to central norepinephrine cells. So far the only empirical basis for this theory is the finding that the activity of dopamine-beta-hydroxylase, a marker enzyme for noradrenaline cells, is lowered in the brains of schizophrenic patients. Thus further confirmation is required. The transmethylation hypotheses assume that hallucinogenic amine metabolites are produced in the body and lead to the appearance of schizophrenic symptoms. Whether or not the occurrence of DMPEA, presumably an oxymethylation product of the dopamine metabolism, is specific for schizophrenics is still open to question; if it is, the meaning of this finding is obscure. Current results leave open the possibility that N-dimethyltryptamine or other N-methylated hallucinogenic biogenic amine metabolites cause the disease; however, this hypothesis is hardly confirmed by positive empirical results.
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PMID:[Biogenic amines and schizophrenia]. 106 94

Recent studies in psychophysiology and neurophysiology strongly indicate that there is an overstimulation of the brain schizophrenia. However, the relationship between overstimulation and schizophrenic symptoms is largely unknown. Neuropathological, anatomical and biochemical data support the conclusion that the schizophrenic syndrome represents a malfunctioning involving at least the neostriatal-thalamus system, perhaps due to an imbalance between dopamine and noradrenaline.
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PMID:Psychophysiological and neurophysiological aspects of schizophrenia. 114 87


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