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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dopamine receptors in the brain play an important role in the treatment of schizophrenia and in the development of tardive dyskinesia. In Parkinson's disease the loss of dopamine innervation and the use of chronic administration of L-DOPA or therapy with dopamine agonists also affects the function of dopamine receptors in brain. Subacute administration of neuroleptic drugs to rodents for a few weeks followed by the withdrawal of the drug induces supersensitivity of dopamine receptors in the striatum. However, the long-term administration of neuroleptic drugs to rodents shows that typical neuroleptic drugs can induce functional supersensitivity of dopamine receptors despite continued administration of drug. In contrast, atypical neuroleptics such as sulpiride, do not appear to induce the same changes in the activity of dopamine receptors. The functional supersensitivity of dopamine receptors produced by repeated administration of neuroleptic is reflected in changes in cholinergic, gamma-aminobutyric acid (GABA), 5-hydroxytryptamine (5-HT) and peptide neuronal systems. Chronic treatment of parkinsonian patients with drugs may obscure the changes in the function of dopamine receptors caused by the disease process. However, chronic administration of L-DOPA to normal rats and to rats with a unilateral lesions of the nigrostriatal pathway induced with 6-hydroxydopamine does not produce a down-regulation of the number of dopamine receptors. Rather, these experiments indicate the development of a functional supersensitivity of dopamine receptors in the absence of any obvious change in the nature of dopamine receptor populations in brain. In conclusion, while pharmacological manipulation, using neuroleptic drugs, produces the expected development of receptor supersensitivity, studies involving chronic treatment with agonists suggests that dopamine receptors do not always respond as would be predicted. It appears that there are aspects of the regulation of dopamine receptors in brain following pharmacological manipulation which remain to be resolved.
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PMID:Chronic pharmacological manipulation of dopamine receptors in brain. 288 59

The long-term administration of neuroleptics causes tardive dyskinesia, which closely resembles levodopa-induced dyskinesias, and is brought about through complex mechanisms which are ill-defined. It is generally believed that the pathogenesis of tardive dyskinesia relates closely to the chronic blockade of dopamine receptor sites and that its pathophysiology results from a hypersensitivity of dopamine receptor sites. In the therapeutic management of neuroleptic-induced tardive dyskinesia, in addition to reserpine and lithium, diazepam, baclofen, or gamma-vinyl-gamma-aminobutyric acid have also been advocated. However, the reported beneficial effects of diazepam and GABA-mimetic agents in ameliorating the symptoms of tardive dyskinesia may occur through a mechanism which does not necessarily link transmission involving both dopamine and GABA. The presence of high concentrations of both cholecystokinin and opioids in the striatum also suggests that these peptides not only may influence dopaminergic transmission, but that they may also be relevant to the psychopathology of schizophrenia and to the therapeutic effects of neuroleptics. Indeed, the acute and chronic administration of neuroleptics alters the levels of cholecystokinin and opioids and their receptors in several brain regions including the striatum. However, neuroleptics also alter the biochemical integrity of neurotensin, neuropeptide Y, substance P and somatostatin, which may also play a role in the overall expression of the neuroleptic-induced extrapyramidal reactions.
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PMID:Dopamine, GABA, cholecystokinin and opioids in neuroleptic-induced tardive dyskinesia. 290 20

Diazepam-binding inhibitor is a novel peptide purified to homogeneity from rat and human brain. Diazepam-binding inhibitor is present, though not exclusively, in gamma-aminobutyric acid (GABA)-containing neurons where it is believed to inhibit GABAergic neurotransmission mediated by GABA by binding to the benzodiazepine-GABA receptor complex. Since an impairment of central GABAergic tone has been postulated to be associated with a number of neuropsychiatric disorders, we measured human diazepam-binding inhibitor immunoreactivity in the cerebrospinal fluid (CSF) of patients suffering from endogenous depression, schizophrenia, and dementia of the Alzheimer's type. Patients with major depression had significantly higher concentrations of human diazepam-binding inhibitor immunoreactivity in CSF when compared with age- and sex-matched normal volunteers, while no difference in CSF diazepam-binding inhibitor immunoreactivity was found in schizophrenics or patients with dementia of the Alzheimer's type when compared with controls. The possibility is discussed that the increased CSF human diazepam-binding inhibitor immunoreactivity observed in depressed patients may represent a functional disinhibition of GABAergic neurotransmission associated with depression.
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PMID:Diazepam-binding inhibitor. A brain neuropeptide present in human spinal fluid: studies in depression, schizophrenia, and Alzheimer's disease. 302 63

The hypothesis of a gamma-aminobutyric acid (GABA) involvement in the pathophysiology of schizophrenia has been recently proposed but not confirmed. As GABA has been shown to affect basal growth hormone (GH) secretion in humans, the assessment of plasma GH response to a GABAergic drug, such as sodium valproate (SV), in schizophrenic subjects might be a tool with which to investigate central GABA activity in this illness. For this purpose, we administered orally 800 mg of SV or placebo to 13 chronic schizophrenics and to 10 normal controls, and measured plasma GH levels before and after the drug administration. SV enhanced basal GH secretion in healthy male volunteers, but not in chronic schizophrenics. These results suggest a defect of the endogenous GABA system in chronic schizophrenia. Whether the reduced responsiveness observed represents a primary defect or a secondary alteration of the GABA system in schizophrenia is as yet unknown.
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PMID:Growth hormone response to sodium valproate in chronic schizophrenia. 308 38

The effect of zinc nutriture and metabolism on brain function has been reviewed. Zinc nutriture and its effect on the concentration and metabolism of essential elements (e.g. zinc, copper, manganese, magnesium, sodium, potassium and calcium) and on the concentration and metabolism of toxic elements (e.g. aluminum and lead) are discussed in relationship to brain function. In addition, possible interrelationships between zinc nutriture and metabolism and its effect on a number of diseases including acrodermatitis enteropathica, Pick's disease, Alzheimer's disease, schizophrenia, fifth day fits, and epilepsy are discussed. Descriptions and comparisons of methods to measure brain zinc are presented. Behavioral changes and the altered brain morphology which have been associated with zinc deficiency are reviewed. Some possible mechanisms for the association of anorexia with zinc deficiency are outlined. Perinatal brain damage produced by early zinc deficiency followed by rehabilitation with adequate zinc appears to be long term, maybe permanent. Interrelationships between zinc nutriture and aspects of neurochemistry are outlined. Some of the neurochemistries discussed include nucleic acid and protein synthesis, cytoskeletal proteins, neurotransmitters (e.g. catecholamines, indoleamines, glutamate, gamma-aminobutyric acid, and neuropeptides), neurotransmitter receptors, 7S nerve growth factor and zinc-binding proteins. Recent evidence linking zinc and neurotransmission is discussed.
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PMID:Zinc and the central nervous system. 330 3

Among the biochemical theories proposed for schizophrenia the best-founded appears to be the dopaminergic theory. Dopaminergic agonists exacerbate schizophrenic symptoms. Neuroleptics, which are the most effective drugs in schizophrenia, are dopaminergic-blocking agents. Other biochemical disorders have been demonstrated in some cases of schizophrenia but results are not always consonant. The presence of abnormal compounds, i.e. methylated derivatives or phenylethylamine, has often been mentioned. Several disorders of enzymes have also been reported, such as a defect in beta-dopamine hydroxylase or an abnormal activity of the MAO which metabolizes the indolamines and catecholamines. Disorders of the metabolism of noradrenaline and serotonin have also been suggested, mainly on experimental evidence. Other compounds have been incriminated, such as endorphins, gamma-aminobutyric acid, lysine-8 vasopressin or prostaglandins. The action of neuroleptics can be ascribed to dopaminergic respector blockade, as a safe approximation. However, the demonstration of several dopaminergic pathways and of several types of receptors makes the understanding of their mode of action all the more difficult that they interplay with many other neurotransmittors.
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PMID:[Biochemistry of schizophrenia and mechanism of action of neuroleptics]. 613 Jun 4

A role for gamma-aminobutyric acid (GABA) in the pathophysiology of schizophrenia was first suggested by Eugene Roberts in 1972. Since then considerable work has been accomplished in both the clinical and basic sciences regarding GABA and schizophrenia. Although it was originally thought that GABA might be useful in treating schizophrenia because of its inhibition of dopaminergic activity, recent data have shown that in certain models GABA has the opposite effect on dopaminergic functions. Regardless of the relationships of GABA to dopamine, neither biochemical nor pharmacological studies have been able to demonstrate a clear and reproducible GABA disturbance in schizophrenia. A number of problems contribute to the difficulty in studying GABA in schizophrenia, including the lack of specific and nontoxic GABA agonists as well as the complexity of the GABA system in brain. Interest in GABA research in schizophrenia appears to have waned, but several areas nevertheless appear promising for clinical investigation.
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PMID:The interaction between GABA and dopamine: implications for schizophrenia. 613 69

Biological studies of the relationships between the schizoaffective disorders, the affective disorders, and schizophrenia suggest that no simple reductionist model is supported by currently available data. Thus, both affective and schizoaffective patients but not schizophrenics, manifest abnormalities such as decreased platelet serotonin (5-HT) uptake, blunted clonidine-induced increase in serum growth hormone, shortened latency of rapid eye movement (REM) sleep, and increased REM density. However, there are some types of studies which show greater similarity between schizoaffective and schizophrenic patients than between schizoaffectives and affectives--e.g., increased cerebrospinal fluid (CSF) norepinephrine levels, increased platelet 5-HT content, and decreased prostaglandin E1-stimulated adenylate cyclase activity. Other types of studies show abnormalities common to all three groups of psychoses--e.g., eye tracking dysfunction, elevated CSF concentration of gamma-aminobutyric acid, and neuromuscular abnormalities. There are also abnormalities that have been reported to be present in only one type of the psychoses. Although none of these findings have been so unequivocally demonstrated that they can be considered to be firmly established, they do suggest that it is premature to conclude that the schizoaffective disorders are subtypes of the affective disorders. The possibility of a continuum model of the psychiatric psychoses of unknown etiology merits further consideration. Further biological studies of a broad range of psychiatric psychoses with inclusion of the schizoaffective categories appear indicated.
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PMID:Biological studies of schizoaffective disorders. 642 46

Gamma-aminobutyric acid (GABA) concentrations were measured in 10 regions of post-mortem brain from control, psychotic and choreic subjects; glutamate decarboxylase (GAD) activities were estimated in substantia nigra. In agreement with earlier observations, agonal status profoundly affected GAD measurements in the substantia nigra but had no effect on GABA levels in any brain region. Although GAD and GABA levels were significantly correlated in nigral tissue from sudden death control and psychotic cases, the association was lost in patients dying slowly. In Huntington's chorea significant reduction in GABA content were observed in the nucleus accumbens, lateral pallidum, subthalamic nucleus, substantia nigra and ventrolateral thalamic nucleus. In psychotic patients there were significant decreases in GABA concentrations in the amygdala and nucleus accumbens. Division of the psychotic group into schizophrenia and schizophrenia-like categories and into early-onset and later-onset cases revealed that GABA levels in the amygdala were diminished in all 4 psychotic subgroups, whereas in the nucleus accumbens the deficit was confined to cases of early-onset schizophrenia.
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PMID:Distribution of GABA in post-mortem brain tissue from control, psychotic and Huntington's chorea subjects. 644 63

The movement disorder tardive dyskinesia is a serious side effect of the long-term treatment of schizophrenia with neuroleptic drugs. Similar symptoms to those of tardive dyskinesia have been observed in Cebus apella monkeys following long-term treatment with neuroleptic drugs, and these monkeys may therefore be a useful animal model of tardive dyskinesia. Motor defects have persisted in these dyskinetic monkeys for periods of 1-6 yr after the cessation of neuroleptic treatment. We report here that in three regions of the brains of dyskinetic monkeys (substantia nigra, medial globus pallidus and subthalamic nucleus) glutamate decarboxylase activities and gamma-aminobutyric acid (GABA) levels are reduced relative to control monkeys that had been treated with neuroleptics but which showed none of the symptoms of tardive dyskinesia. These results suggest that alterations in the GABA neurone system are involved in neuroleptic drug-induced tardive dyskinesia.
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PMID:Association with persistent neuroleptic-induced dyskinesia of regional changes in brain GABA synthesis. 672 89


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