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)

A study of the activity of leukocyte enzymes in the blood of patients with nuclear forms of schizophrenia (52 cases) and in patients with circular schizophrenia (22 cases) depicted the following conditions. In the group of malignant schizophrenia, irrespective of the stage of the disease and in the group of circular forms there was a definite drop in the activity of cytochromoxidase, succinatedehydrogenase and MAO, while as the activity of the ATP-ase and peroxidase was increased. Supplementary animal experiments in vitro and in vivo made it possible to assume that these changes are due to the so-called serum factor.
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PMID:[The effect of schizophrenic patients serum on the activity of several leukocyte enzymes]. 17 27

The purpose of this controlled clinical trial was to demonstrate possible correlations between changes in bioenergetic metabolism and psychotropic drug administration in the treatment of functional psychosis. The study included twenty-six patients, eleven with schizophrenia, three with chronic atypical depression and twelve with drug-resistant endogenous depressions. All patients were kept on continuous psychotropic medication for at least 3 weeks before starting the trial, and piracetam was given additionally in a fixed dosage of 2400 mg daily; the same number of identical capsules was given during the pre- and post-treatment placebo periods. Psycho-pathological evaluation of the patients was by the BPRS; clinical and biochemical data were evaluated statistically by the analysis of regression. The results show that in schizophrenic patients an improvement was observed in those cases who had improved biochemically, i.e. where the ATP values had increased. In drug-resistant depressions there was a rapid and significant clinical improvement after piracetam co-administration, and this went in step with a significant rise in ATP levels.
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PMID:Biological correlates of piracetam clinical effects in psychotic patients. 48 20

Eleven schizophrenic patients and nine normal controls were studied using in vivo 31Phosphorous magnetic resonance spectroscopy (31P MRS) to test the hypothesis of metabolic asymmetry in the temporal lobes in schizophrenia. The controls did not demonstrate any asymmetry of phosphorous metabolite ratios, percentage of phosphorous metabolites, or pH. In the schizophrenics, however, phosphocreatine/beta-adenosine triphosphate (PCr/beta-ATP) and phosphocreatine/inorganic phosphate (PCr/Pi) effects appeared to primarily reflect higher ratios on the right side, while the percentage of beta-ATP appeared to primarily reflect higher relative concentrations in the left temporal lobe. Moreover, significant negative correlations were noted between total Brief Psychiatric Rating Scale scores and PCr/beta-ATP in both the right and left temporal lobes. These results support the hypothesis of an asymmetric distribution of 31P metabolites in the temporal lobe of schizophrenic patients, and also show an association between temporal lobe phosphorous metabolism and the severity of psychiatric symptomatology.
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PMID:31Phosphorus magnetic resonance spectroscopy of the temporal lobes in schizophrenia. 139 Dec 94

In vivo 31Phosphorous magnetic resonance spectroscopic imaging (31P MRSI) was performed on 18 chronic schizophrenic patients and 14 normal controls to determine if there was asymmetry of high-energy phosphorous metabolism in the temporal lobes of schizophrenic patients. Temporal lobe phosphorous metabolites were also correlated with severity of psychiatric symptomatology as assessed by the Brief Psychiatric Rating Scale (BPRS). Schizophrenics demonstrated significantly higher right relative to left temporal phosphocreatine/adenosine triphosphate (PCr/ATP), phosphocreatine/inorganic phosphate (PCr/Pi), and PCr as well as significantly lower right relative to left temporal ATP. There were no asymmetries of temporal lobe phosphorous metabolites in the control group. In addition, both left temporal PCr and the degree of asymmetry of temporal lobe PCr were highly correlated with the thinking disturbance subscale of the BPRS. This study provides further support for temporal lobe metabolic asymmetry in schizophrenia and its possible association with clinical symptoms.
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PMID:Asymmetry of temporal lobe phosphorous metabolism in schizophrenia: a 31phosphorous magnetic resonance spectroscopic imaging study. 749 21

Increased levels of dopamine have been associated with schizophrenia and mania; conversely, decreased levels of dopamine are associated with depression. Since the main mechanism for the termination of dopamine's pharmacological action is by re-uptake into the presynaptic cell, the speed of dopamine transport dramatically influences the concentration of dopamine present in the synaptic cleft, which in turn could determine brain disorders. Our preliminary studies have found that ATP can stimulate dopamine transport in rat synaptosomal preparation. We have also observed this ATP-regulated moiety of the dopamine uptake system when tested in PC12 cells. The large magnitude of ATP stimulation suggests that this dopamine uptake pathway may be important in the etiology and treatment of brain disorders. In order to test the relevance of ATP-stimulated dopamine uptake, we tested the effect of lithium salts on this system. Lithium chloride, one of the first drugs used in the treatment of mania, has become one of the most important agents utilized for the treatment of manic-depression and many schizoeffective disorders. Unfortunately, despite all efforts that have been made to explain lithium's mode of action, a clear cut biochemical mechanism has not been defined. We have found that lithium chloride, at therapeutic levels, is able to stimulate the ATP-regulated component of the dopamine uptake system by 49%. The further enhancement of dopamine re-uptake by lithium ions is consistent with its therapeutic effect. It is suggested that any substance that facilitates dopamine re-uptake could be of great importance in defining a useful treatment for mania and schizophrenia, as well as depression.
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PMID:Li+ stimulates ATP-regulated dopamine uptake in PC12 cells. 775 92

Recent research in computational neuroscience has suggested that psychosis associated with disturbed catecholamine neurotransmission may result from disturbances in the gain parameters of neural networks that these same secondary neurotransmitters are thought to control. We propose a mathematical model based upon cooperativity theory used in thermodynamics to explain how the gain parameter that momentarily increases the effect upon the post-synaptic cell of a given weighted connection from the presynaptic cell could be instantiated in the fluctuating electrical conductance of the dendrite of a neuron without requiring extensive ion transport or utilization of the ATP energy cycle. More specifically we propose that catecholamine neurotransmission serves to maintain the dendrite in a cooperative state with regard to changes in electrical conductance due to impulse traffic alone. In this way we supply the neuron with an activity driven gain parameter that not only increases volume of neuronal output at very low energy cost but that also upscales cooperative effects at the mechanico-chemical level of the dendrite to the network level itself. An important implication of this model is that two extreme states for dendritic electrical conductance will occur if cooperativity is lost at the level of catecholamine depletion or excess due to drug effects. These are the AND gate effect in which dendritic conductance is so low that the neuron requires extensive synaptic activity in order to output significantly. We correlate this state with negative symptoms in schizophrenia and psychomotor retardation in depression as well as the rigidity in Parkinsonism. The other extreme is represented by the OR gated dendrite in which conductance is so high that even noisy input to the dendrite will lead to significant nerve cell output. We correlate this condition with the positive symptoms of schizophrenia, the agitated features of psychotic depression and the tremors of Parkinsonism.
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PMID:A theory of cooperativity modulation in neural networks as an important parameter of CNS catecholamine function and induction of psychopathology. 787 Feb 71

Erythrocyte ATP-ase activities were determined in 32 drug-free patients with depression in the course of affective illness, during acute episode, in 24 drug-free patients with schizophrenia, during exacerbation of the illness, and in 25 healthy control subjects. In both depression and schizophrenia, the activities of all three ATP-ases studied (Na-K ATPase, Mg ATPase, Ca-Mg ATPase) were significantly lower than in control subjects. No difference was found between patients with depression in the course of bipolar and unipolar affective illness. In patients with schizophrenia, the activity of Na-K ATPase was lower in the paranoid type of the illness. The results are discussed in the light of contemporary biochemical concepts of major psychoses.
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PMID:Decreased activity of erythrocyte membrane ATPases in depression and schizophrenia. 796 52

As compared to normal people, the lymphocytes of patients with schizophrenia were found to have an impairment of ATP.Mg-dependent protein phosphatase activation. More importantly, the impaired protein phosphatase activation in the lymphocytes of schizophrenic patients could be consistently and completely restored to normal by exogenous pure protein kinase FA/glycogen synthase kinase-3 alpha (kinase FA/GSK-3 alpha) (the activating factor of ATP.Mg-dependent protein phosphatase), indicating that the molecular mechanism for the impaired protein phosphatase activation in schizophrenic patients may be due to a functional loss of kinase FA/GSK-3 alpha. Immunoblotting and kinase activity analysis in an anti-kinase FA/GSK-3 alpha immunoprecipitate further demonstrate that both cellular activities and protein levels of kinase FA/GSK-3 alpha in the lymphocytes of schizophrenic patients were greatly impared as compared to normal controls. Statistical analysis revealed that the lymphocytes isolated from 37 normal people contain kinase FA/GSK-3 alpha activity in the high levels of 14.8 +/- 2.4 units/mg of cell protein, whereas the lymphocytes of 48 patients with schizophrenic disorder contain kinase FA/GSK-3 alpha activity in the low levels of 2.8 +/- 1.6 units/mg, indicating that the different levels of kinase FA/GSK-3 alpha activity between schizophrenic patients and normal people are statistically significant. Taken together, the results provide initial evidence that patients with schizophrenic disorder may have a common impairment in the protein levels and cellular activities of kinase FA/GSK-3 alpha, a multisubstrate protein kinase and a multisubstrate protein phosphatase activator in their lymphocytes.
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PMID:Dysfunction of protein kinase FA/GSK-3 alpha in lymphocytes of patients with schizophrenic disorder. 853 May 29

The possible implication of P2-purinoceptors in brain functions is reviewed. Involvement of P2-purinoceptors in memory and learning (Section 2) is suggested by ATP release from hippocampal slices [Wieraszko, A., Goldsmith, G. and Seyfried, T. N. (1989) Brain Res. 485, 244-250], induction of fast synaptic currents in cultured hippocampal neurons [Inoue, K., Nakazawa, K., Fujimori, W. and Takanaka, A. (1992a) Neurosci. Lett. 134, 294-299] and long-lasting enhancement of the population spikes [Wieraszko, A. and Seyfried, T. N. (1989) Brain Res. 491, 356-359; Nishimura, S., Mohri, M., Okada, Y. and Mori, M. (1990) Brain Res. 525, 165-169; Fujii, S., Kato, H., Furuse, H., Ito, K., Osada, H., Hamaguchi, T. and Kuroda, Y. (1995) Neurosci, Lett. 187, 130-132], as well as ATP release on glutamate stimulation to evoke an increase in intracellular Ca2+ in hippocampal cells [Inoue, K., Koizum, S. and Nakazawa, K. (1995) NeuroReport 6, 437-440]. Moreover, mRNAs for certain types of P2x-purinoceptors are present in the hippocampus [Collo, G., North, R. A., Kawashima, E., Merlo-Pich, E., Neidhart, S., Surprenant, A. and Buell, G. (1996) J. Neurosci. 16, 2495-2507]. It is likely, therefore, that ATP may be involved in modulation of synaptic efficiency in the hippocampus. The implication of ATP in schizophrenia is suggested by the fact that antipsychotic drugs inhibit ATP-evoked responses in PC12 cells [Koizumi, S., Ikeda, M., Nakazawa, K., Inoue, K., Ito, K. and Inoue, K. (1995b) Biochem. Biophys. Res. Commun. 210, 624-630] without blocking the action of dopamine D2 receptors. Involvement of P2-purinoceptors in Sections 4 ("Pain and cognition") and 5 ("Central regulation of the autonomic system") are also discussed.
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PMID:Implication of ATP receptors in brain functions. 901 23

An apparent disturbance was revealed in microhaemodynamics of patients diagnosed as having schizophrenia (n = 210) which was more pronounced in continuously progredient form of the above medical condition. An increase in conjunctival indexes, polymorphic character of capillaries, decrease in numbers of capillary loops were revealed by biomicroscopy of the bulbar conjunctiva and capillaroscopy respectively. The patients showed lowering of ATP level and rise in the content of cathodic LDG4-LDG5 fractions, accumulation in blood of lactic and pyruvic acids.
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PMID:[Microhemodynamics and energy metabolism in schizophrenia patients]. 922 Nov 48


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