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)

The causes of schizophrenia are unknown, but there is evidence linking subtle deviations in neural development with schizophrenia. Embryonic brain development cannot be studied in an adult with schizophrenia, but neurogenesis and early events in neuronal differentiation can be investigated throughout adult life in the human olfactory epithelium. Our past research has demonstrated that neuronal cultures can be derived from biopsy of the human adult olfactory epithelium. In the present study, we examined mechanisms related to neurogenesis and neuronal differentiation in adults with schizophrenia versus well controls. Forty biopsies were collected under local anaesthesia from ten individuals with DSM III-R schizophrenia and ten age- and sex-matched well controls. All patients, except one, were receiving antipsychotic medication at the time of the biopsy. Immunostaining for neuronal markers indicated that neurogenesis occurred in the biopsies from both patients and controls since all contained cells expressing tubulin and/or olfactory marker protein. The major findings of this study are: 1. biopsies from patients with schizophrenia showed a significantly reduced ability to attach to the culture slide: 29.9% of patient biopsies attached compared to 73.5% of control biopsies; 2. biopsies from patients with schizophrenia had a significantly greater proportion of cells undergoing mitosis: 0.69% in the patients compared to 0.29% in the controls; and 3. dopamine (10 microM) significantly increased the proportion of apoptotic cells in the control cultures but significantly decreased the proportion in patients' cultures.
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PMID:Altered adhesion, proliferation and death in neural cultures from adults with schizophrenia. 1063 59

Genetic predisposition and environmental factors such as perinatal complications are believed to contribute to the etiology of schizophrenia, a disorder involving enhanced CNS dopaminergic activity. This study used a rat model to test whether genetic factors and a minor birth complication, i.e. Caesarean section (C-section) birth, interact in producing longterm effects on dopamine-mediated behavior. For this, we compared the effects of vaginal and C-section birth on amphetamine (AMPT)-induced locomotor activity in strains of rats differing in genetic composition. In Sprague-Dawley rats, C-section birth increased AMPT-induced locomotion compared with vaginal birth. By contrast in Lewis rats, C-section birth reduced AMPT-induced locomotion compared with vaginal birth. In Fischer rats, AMPT-induced locomotion was increased by C-section under maternal anesthesia but decreased by C-section after maternal decapitation, compared with vaginal birth. It is concluded that a minor birth complication like C-section can have differing long-term effects on dopaminergic function in the rat, depending on the genetic composition of the individual.
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PMID:Genetic factors modulate effects of C-section birth on dopaminergic function in the rat. 1071 28

A 33 year-old man weighting, 93 kg with schizophrenia underwent repeated electroconvulsive therapy (ECT) under general anesthesia with thiamylal 200 mg and suxamethonium 80 mg. On his fourth ECT, he developed ventricular tachycardia (VT) immediately after the treatment under general anesthesia with the same agents. The duration of VT was approximately 30 s. The VT returned to sinus rhythm without any special treatment. We speculate that light anesthesia with a small amount of thiopental associated with release of serum potassium caused by suxamethonium induced increased release of catecholamine by ECT to cause VT. After that incident, the patient underwent ECT six times under general anesthesia with thiamylal 250 mg and vecuronium 8 mg, in combination with preventive injection of magnesium sulfate 20 g without any cardiovascular complications. We conclude that the anesthetic management of patients undergoing ECT under general anesthesia should be paid a careful attention for cardiovascular instability, even if they do not have any heart diseases.
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PMID:[A case of ventricular tachycardia immediately after electroconvulsive therapy in a schinzophrenic patient]. 1121 51

The effects of social isolation on prepulse inhibition of acoustic startle (PPI), electrophysiology and morphology of subicular pyramidal neurons and the densities of interneuronal sub-types in the hippocampal formation were examined. Wistar rats (male weanlings) were housed socially (socials, n=8) or individually (isolates, n=7). When tested eight weeks later, PPI was lower in isolates. Rats then received terminal anaesthesia before slices of hippocampal formation were made in which the electrophysiological properties of a total of 108 subicular neurons were characterized. There were no differences in neuronal sub-types recorded in socials compared with isolates. Intrinsically burst-firing and regular spiking pyramidal neurons were examined in detail. There were no differences in resting membrane potential or input resistance in isolates compared with socials but action potential height was reduced and action potential threshold raised in isolates. A limited morphological examination of Neurobiotin-filled intrinsically burst-firing neurons did not reveal differences in cell-body area or in number of primary dendrites. Sections from the contralateral hemispheres of the same rats were stained with antibodies to calretinin, parvalbumin and the neuronal isoform of nitric oxide synthase (nNOS). In isolates, the density of calretinin positive neurons was increased in the dentate gyrus but unchanged in areas CA3, CA1 and subiculum. Parvalbumin and nNOS positive neuronal densities were unchanged. Hence in rats with environmentally induced reductions in PPI there are structural and functional abnormalities in the hippocampal formation. If the reduction in PPI stems from these abnormalities, and reduced PPI in rats is relevant to schizophrenia, then drugs that correct the reported electrophysiological changes might have antipsychotic effects.
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PMID:Structural and functional abnormalities of the hippocampal formation in rats with environmentally induced reductions in prepulse inhibition of acoustic startle. 1124 47

The anesthesia for sismotherapy is characterized by its briefness and repetitiveness, resulting in several imperatives: anesthesia of short duration, deep narcosis with muscular relaxation and ambulatory character. Thus anesthesic drugs should have a fast onset of action, in order to obtain a rapid and as alert as possible post anesthesia awakening. The objective of this study is to compare two anesthesic drugs: propofol versus thiopentone. We included in this study patients referred to our unit by the psychiatric service for sismotherapy, which was carried on under general anesthesia in the awakening room of the anesthesia department of Ibn Rochd University hospital. 7 of our patients received sismotherapy for schizophrenia, 2 for acute mania and 1 for suicidal depression. A total of 40 sessions of sismotherapy were analyzed, distributed in two groups: group I (n = 20): benefitted of a general anesthesia by thiopentone, the dose was 2 to 3 mg/kg; group II (n = 20): benefitted of general anesthesia by propofol, the dose was 1 to 1.5 mg/kg. Sismotherapy was carried out only once narcosis was considered as deep. To monitor our patients we used electrocardioscope and pulpe oxymeter. We evaluated the quality and especially the time of onset of anesthesia, its duration, the quality of narcosis, the degree of muscular relaxation, respiratory and cardiovascular parameters as well as side effect linked to anesthesia drugs and sismotherapy. Analysis of the results showed that the quality of anesthesia was excellent for both groups. The necessary dose for narcosis was 202 mg for thiopentone and 167 mg for propofol, time of onset of narcosis was 30 seconds for propofol and 45 seconds for thiopentone, anesthesia and the quality of muscular relaxation were considered deep for the two groups. Many authors showed that propofol is the most efficient agent in anesthesia for sismotherapy due to its brief delay of action and faster reversibility. As for thiopentone despite its convulsive properties and poor hemodynamic tolerance, it still is a good hypnotic in anesthesia for sismotherapy when administered at appropriate dose by slow injection. This is due on the one hand to easy administration, lesser incidence of side effects and on the other hand to brief duration of action and low cost. We conclude that thiopentone can be recommended in anesthesia for sismotherapy owing to good properties: deepness of anesthesia, good awakening, tolerance and lower cost.
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PMID:[Anesthesia for electroconvulsive therapy: propofol versus thiopental]. 1148 51

Electroconvulsive therapy (ECT) has antidepressive and antipsychotic effects. Since being introduced in Italy in 1938, its mode of action has still not been clarified. Treatment modalities have changed in many ways. ECT, in which a generalized epileptic seizure is provoked by electrical stimulation of the brain, is performed under short intravenous anesthesia and muscle relaxation. Considering careful previous clinical examination and anesthesiological and internal counterindications, ECT is a very safe form of treatment. Single cases of persisting memory impairment were described after the formerly common bilateral sinus wave stimulation. However, recent developments such as brief pulse stimulation, unilateral electrode placement, and individual stimulus titration (on the basis of EEG monitoring) make memory impairment as a consequence of ECT a rare event which mostly remits completely in 4-8 weeks. Today, ECT is performed mainly in patients suffering from severe, therapy-resistant affective or schizophrenic disorders. Pernicious catatonia and the neuroleptic malignant syndrome are emergency indications. Adequate ECT treatment requires a series of 6-12 individual sessions (every second or third day). In therapy-resistant depression, for which the greatest number of data are available, the response rate lies between 50 and 60%. This has been confirmed by a descriptive analysis of all ECT treatments at the Department of Psychiatry, University of Vienna, between 1994 and 2000. There is a need for controlled studies on continuation therapy subsequent to successful ECT.
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PMID:[Use of electroconvulsive therapy in psychiatry]. 1157 99

We experienced anesthetic management for ECT in a patient with psychiatric disease during the third trimester of pregnancy. The 24 year-old patient had been on oral antipsychotics prescribed to treat schizophrenia for ten years. Her signs and symptoms deteiorated during pregnancy in spite of increased doses of antipsychotics. With tocolytic agent administered intravenously, anesthesia was induced by intravenous thiamylal immediately followed by intravenous suxamethonium for muscle relaxation. Alternative current was applied on both side of the head after the sufficient anesthesia had been obtained. The patient received intermittent mandatory ventilation by breathing mask with 100% oxygen during the procedure. Along with monitoring of maternal hemodynamic variables and arterial oxygen saturation (Spo2), fetal heart rate and uterine contraction were recorded by cardiotocogram throughout the procedure. At the first two treatments, the patient showed neither significant uterine contraction nor fetal heart rate changes. At the third treatment, continuous uterine contraction refractory to tocolysis was recorded for six minutes, resulting in fetal bradycardia. At the sixth treatment, general anesthesia was induced and maintained by sevoflurane in oxygen followed by suxamethonium for muscle relaxation. The uterine contraction was remarkably diminished and fetal heart rate remained unchanged during the procedure. In conclusion, inhalation anesthesia is beneficial for ECT in the last stage of pregnancy to reduce uterine contraction by potential uterine relaxation effect of anesthetics.
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PMID:[Anesthesia for electroconvulsive therapy during pregnancy--a case report]. 1159 22

NMDA antagonists provide the best pharmacological model of psychosis-related schizophrenia. Data from circuit analysis of the effects of the antagonism of NMDA receptors in the CA1 region of the hippocampus of rats in vitro suggest a hypothesis concerning cortical circuit dysfunction responsible for NMDA antagonist-dependent psychosis, relevant to the psychosis associated with schizophrenia. The NMDA antagonists may act by causing a selective, partial, disinhibition of cortical projection cells. The effects are partially due to the partial role of NMDA-dependent transmission in the excitatory glutamate drive of interneurons. Characterization of the selectivity is incomplete, but includes disinhibition of the recurrent inhibitory circuit and is concentration-sensitive. It may result from differences in NMDA receptors (NMDARs) on interneurons. At higher concentrations, antagonism of all NMDA-dependent transmission results in anesthesia. At low concentration, selective blockade of NMDA-dependent LTP of the recurrent inhibitory circuit may disrupt particular aspects of information processing involving learning and/or memory, consistent with the generation of abnormal associations. An endogenous peptide, NAAG, is shown to antagonize NMDARs in a manner similar to known psychotogenic agents like ketamine or phencyclidine. Finally, mechanisms that could enhance NMDAR function are discussed as possible therapeutic strategies for psychosis.
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PMID:Circuit analysis of NMDAR hypofunction in the hippocampus, in vitro, and psychosis of schizophrenia. 1173 9

NMDA glutamate receptor antagonists are used in clinical anesthesia, and are being developed as therapeutic agents for preventing neurodegeneration in stroke, epilepsy, and brain trauma. However, the ability of these agents to produce neurotoxicity in adult rats and psychosis in adult humans compromises their clinical usefulness. In addition, an NMDA receptor hypofunction (NRHypo) state might play a role in neurodegenerative and psychotic disorders, like Alzheimer's disease and schizophrenia. Thus, understanding the mechanism underlying NRHypo-induced neurotoxicity and psychosis could have significant clinically relevant benefits. NRHypo neurotoxicity can be prevented by several classes of agents (e.g. antimuscarinics, non-NMDA glutamate antagonists, and alpha(2) adrenergic agonists) suggesting that the mechanism of neurotoxicity is complex. In the present study a series of experiments was undertaken to more definitively define the receptors and complex neural circuitry underlying NRHypo neurotoxicity. Injection of either the muscarinic antagonist scopolamine or the non-NMDA antagonist NBQX directly into the cortex prevented NRHypo neurotoxicity. Clonidine, an alpha(2) adrenergic agonist, protected against the neurotoxicity when injected into the basal forebrain. The combined injection of muscarinic and non-NMDA Glu agonists reproduced the neurotoxic reaction. Based on these and other results, we conclude that the mechanism is indirect, and involves a complex network disturbance, whereby blockade of NMDA receptors on inhibitory neurons in multiple subcortical brain regions, disinhibits glutamatergic and cholinergic projections to the cerebral cortex. Simultaneous excitotoxic stimulation of muscarinic (m(3)) and glutamate (AMPA/kainate) receptors on cerebrocortical neurons appears to be the proximal mechanism by which the neurotoxic and psychotomimetic effects of NRHypo are mediated.
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PMID:Receptor mechanisms and circuitry underlying NMDA antagonist neurotoxicity. 1180 44

England's High Court of Justice, Family Division, dismissed a health authority's application for a judicial declaration that a proposed diagnostic procedure on a mentally ill woman incapable of consent was lawful, because such a declaration "might be an unfortunate signal to others in the future that it was appropriate, as a matter of good medical practice, for the implementation of such procedures to be delayed pending the outcome of a costly application to the court." H, age 25, suffered from schizophrenia. Doctors suspected that she had a brain tumor and wanted to give her a diagnostic CT brain scan. H would require heavy sedation under general anesthesia and an injection of the contrast medium. H hated needles, would likely be non-cooperative, and lacked any capacity for informed consent. Her parents strongly supported the procedure as did the Official Solicitor, who represented H as guardian ad litem. The Official Solicitor, however, opposed a judicial application as inappropriate, because the doctors had already decided that the brain scan was in H's best interest. The court found no distinction between therapeutic and diagnostic procedures. In this circumstance the court agreed with the Official Solicitor that a judicial declaration would not be appropriate. The court found that the proposed brain scan was clearly in H's best interests. Accordingly, as the court quoted from Re F (Sterilisation: Mental Patient), "a doctor can lawfully operate on, or give other treatment to, adult patients who are incapable, for one reason or another, of consenting to his doing so, provided that the operation or other treatment is in the best interests of such patients."
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PMID:Re H (Mental Patients: Diagnosis). 1204 Oct 93


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