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)

Four cases of resistant Schizophrenia treated with valproate association with different neuroleptic drugs (thioridazine in three cases and loxapine in one) are presented. After a mean period of three months with this treatment, clinical improvement, consisting in a reduction of positive symptoms, as measured by the BPRS, and a normalization of hostile/disruptive behavior, was observed, and hospital discharge was possible. Reduction of symptoms was still present after a follow-up of 4 to 24 months. As valproate is a drug with gabaergic properties, a GABA involvement in the pathogenesis of schizophrenia is discussed. The association of valproate to neuroleptic drugs should be considered in the treatment of resistant Schizophrenia.
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PMID:Treatment of resistant schizophrenia with valproate and neuroleptic drugs. 257 9

The binding of [3H]nipecotic acid, a ligand for labelling GABA uptake sites in brain, was measured in left and right frontal cortex, polar temporal cortex, hippocampus and amygdala from control and schizophrenic postmortem brains. In schizophrenic brains, single concentration [3H]nipecotic acid binding was reduced bilaterally in amygdala and hippocampus and on the left side only in polar temporal cortex. These data suggest that GABA neurones are involved in the cerebral atrophy of schizophrenia and, in agreement with other studies, that this process is most pronounced in left temporal cortex.
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PMID:Reduced GABA uptake sites in the temporal lobe in schizophrenia. 261 32

Following a historical review and critical appraisal of the literature (problems of definition, selection, frequency, etiology, relation and classification) clinical findings from a series of retrospective and prospective studies (four samples with altogether 47 epileptic patients) are presented and discussed, as well as the results of EEG, CT and other relevant investigations. (1) 'Schizophrenia-like' interictal (periictal) psychoses in the epilepsies, which are not rare, appear to be true schizophreniform (= schizophrenic-accentuated) syndromes in a setting of 'clear' consciousness. There is no case of alternative psychosis and EEG 'forced normalization'. (2) Between schizophrenic-accentuated syndromes associated with regularly symptomatic epilepsies and genuine (endogeneous) schizophrenias, there are quantitative but no qualitative differences. Often there is a congruence and no possibility of differentiating in the transverse study. This is also true both for the affective and the cognitive disturbances ('structure of consciousness'); the latter are not suitable for separating the psychopathological syndromes of epilepsies. A discrimination between 'genuine' and 'symptomatic' schizophrenia is no longer meaningful. (3) A true (hereditary) coincidence of (genuine) epilepsy and schizophrenia occurs obviously very seldom. (4) Numerous findings are presented, concerning the conditions in which schizophrenic-accentuated syndromes appear. The following relevant factors are discussed: hereditary, latency, duration of illness, type and frequency of seizures, type and localization of EEG foci, type, extent and topography of brain lesions, quantity and quality of psychopathological findings as well as 'organic' psychosyndromes. The possible triggering of psychoses by psychosocial factors, low intelligence, chronic folate deficiency and other specific risk factors and the role of neurotransmitter disorders (GABA hypotheses) are discussed. Finally proposals are made concerning prevention and therapy. Especially often diagnosed non-alternative schizophrenic syndromes in epileptic patients must be controlled by blood levels of antiepileptics. There is a transitional rank, constituted by defined determinants between the poles epilepsy and schizophrenia or a converging course of those syndromes. The results should lead to more frequent EEG and CT eventual magnetic resonance imaging or positron emission tomography-investigations in schizophrenic patients.
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PMID:Schizophrenic syndromes in epilepsies. 266 7

1. Some disturbances in brain amino acids are reported with regard to pathological changes in schizophrenia: a reduction in GABA content and a reduced activity at some glutamatergic synapses. 2. Comparison of post-mortem brain tissue from control subjects and schizophrenic patients can provide evidence for amino acid alterations in disease. 3. The present study was undertaken to measure free amino acid concentrations in 20 brain regions obtained at autopsy, from normal persons and schizophrenics. Amino acids were extracted, esterified and separated by gas chromatography. 4. The distribution and levels of amino acids in normal persons is in accordance with similar values reported in human post-mortem brain samples by other investigators. 5. The differences in amino acids found in schizophrenic brain samples support the view of disturbed neurotransmission especially with regard to GABAergic and glutamatergic systems in schizophrenia and suggest the possible involvement of other amino acids as well.
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PMID:Free amino acid level determinations in normal and schizophrenic brain. 274 56

Neurochemical indices of dopaminergic function were assessed in basal ganglia of post-mortem brains of control subjects and schizophrenic patients who had been rated in life for the presence of movement disorder and neuroleptic intake. In schizophrenics who had been treated chronically with doses of neuroleptics, concentrations of dopamine D2 receptors were significantly increased above controls, whereas dopamine D1 receptors and dopamine metabolism were unchanged. Increased D2 receptors were also observed in basal ganglia of drug-free patients. Concentrations of dopamine D1 and D2 receptors in schizophrenics with movement disorder. Moreover, no relationship was found between dopamine receptor levels and the severity of movement disorder. Concentrations of the dopamine metabolite homovanillic acid were increased in the putamen and nucleus accumbens in a small number of patients with movement disorder compared with controls or patients without movement disorder. No changes were observed in markers of cholinergic and GABA-containing neurones. The present findings are not consistent with a "dopamine receptor hypersensitivity" concept of movement disorder in schizophrenia.
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PMID:Chemical and structural changes in the brain in patients with movement disorder. 286 Jun 53

Movement abnormalities in neuroleptic-treated, psychiatric patients are classified as (a) initial syndromes, including dystonia, parkinsonism, and hyperkinetic abnormalities such as initial dyskinesia (ID) and akathisia, all of which are related to the neuroleptic dose and can be considered as overdose phenomena; (b) tardive syndromes, mainly the classic tardive dyskinesia (TD) syndrome, more seldom tardive akathisia and tardive dystonia, which may all develop or aggravate after withdrawal of neuroleptic treatment; and (c) age-related, spontaneous dyskinesia, akathisia, and dystonia, and schizophrenia-related, hyperkinetic, often stereotyped, movements and restlessness. ID and TD can occur simultaneously, and may depend, at least partially, on identical mechanisms. The pathophysiology of TD is still not clear, and the traditional dopamine (DA) hypersensitivity model seems inadequate. Animal experiments suggest that blockade of some DA receptors in the brain (e.g., in ventromedian striatum) may counteract hyperkinesia and produce parkinsonism, while a concomitant blockade of other similar receptors in other brain regions (e.g., in anterodorsal striatum) may aggravate movements. This offers an explanation for the concomitant occurrence of parkinsonism and hyperkinetic movement abnormalities (ID and akathisia) relatively early in a neuroleptic treatment, and may also contribute to the understanding of the pathophysiology of TD. It is concluded that pathophysiologically TD is a heterogeneous syndrome depending on a subtle balance between several neurotransmitters in the brain, including DA receptor blockade and hypersensitivity of DA and GABA receptors.
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PMID:Pathophysiological mechanisms underlying tardive dyskinesia. 286 Jun 66

There are some evidences to propose blood platelets as a model of bioaminergic neurons. Similarities between platelets and neurons are particularly important with respect to serotonin metabolism but now it is possible to extend this model to other neurotransmitters such as dopamine, GABA, glutamate... The reason for these similarities may be due to the common embryonic origin of these two very different cell types. Some changes of platelet functions are observed in psychiatric syndromes. For example: serotonin uptake, bioamine storage, enzymatic activities are modified in different types of depression and schizophrenia, infantile autism, neurologic diseases (migraine, chorea, Down syndrom). Furthermore, psychotropic drugs also alter the platelet functions. Recently, the discovery of neuro-endocrine disorders in psychiatric diseases has led to the proposal of platelets as a model in neuro-endocrinology. Some arguments can be developed to support this hypothesis. In biological psychiatry, the platelet model seems actually useful essentially in the classification of psychiatric diseases, the management of treatments and the study of new psychotropic drugs. However methodologic difficulties still presently limit the development of this model.
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PMID:[Blood platelets: neuronal model in psychiatric disorders]. 286 6

For two decades it has been hypothesized that schizophrenia and depression are related to alterations in the activity of specific neurotransmitters in brain; to a great extent, these theories are based on the assumed mode of action of antipsychotic and antidepressant drugs. With the available knowledge of how panic anxiety can be effectively treated (and elicited) with drugs, it is now reasonable to formulate hypotheses also regarding the contribution of central neurotransmitters to the generation of panic. As will be discussed in this brief review, three substances seem to be of particular importance in this context: serotonin, noradrenaline and GABA. In view of this concept, the putative mode of action of the atypical benzodiazepine derivative alprazolam, which in contrast to other benzodiazepines has been attributed effectiveness in the treatment of panic, will also be discussed.
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PMID:Brain neurotransmission in panic disorder. 289 Feb 66

Previous electrophysiological studies have demonstrated that non-dopaminergic (non-DA) neurons within the substantia nigra pars reticulata (SNR) are extremely sensitive to the inhibitory effects of GABA and GABA-mimetic drugs, including benzodiazepines, whereas dopaminergic (DA) neurons in the substantia nigra pars compacta (SNC) are less sensitive to these compounds and may be influenced indirectly by SNR neurons. The interactions between A10 DA and non-DA neurons within the adjacent ventral tegmental area (VTA) are not as well characterized. In the present experiments, single unit recording and microiontophoretic techniques were used to determine the effects of benzodiazepines on DA and non-DA neurons in the VTA of chloral hydrate anesthetized rats. Diazepam, administered intravenously (i.v.), potently inhibited non-DA, SNR-like cells within the VTA. The effects of diazepam on A10 DA cells were more variable than those observed on non-DA, SNR-like cells in this region, but 77% of such cells showed moderate to marked excitation. Both of these effects were reversed by the benzodiazepine antagonist Ro 15-1788; on many cells, this agent produced marked rebound effects beyond the original basal firing rates. However, when administered alone, Ro 15-1788 exerted no effect on either cell population. Microiontophoretic administration of the benzodiazepines chlordiazepoxide and flurazepam resulted in marked inhibition of non-DA SNR-like cells, but produced either mild inhibition or no effect on A10 DA cells; excitation of DA cells was never observed even though the same neuron was excited by i.v. diazepam. These findings suggest that benzodiazepines act directly upon non-DA, SNR-like cells in the VTA to produce inhibition of activity and a disinhibition of A10 DA cells. This relationship makes it unlikely that benzodiazepines would enhance feedback inhibition of DA cells following neuroleptic administration. In fact, when administered following haloperidol, i.v. diazepam failed to reverse haloperidol-induced increases of A10 DA cell firing; if anything, diazepam further depolarized the cell. If antipsychotic drugs produce their clinical effects, in part, by inducing depolarization inactivation of DA cells, then benzodiazepines might be a useful adjunctive therapy in the treatment of schizophrenia.
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PMID:Inhibition of non-dopamine cells in the ventral tegmental area by benzodiazepines: relationship to A10 dopamine cell activity. 289 84

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


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