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)

Some evidence points towards a possible autoimmune role in the aetiology of schizophrenia. Experimental findings provide contradictory results regarding abnormalities in cytokine production in this disorder. In the present study we tested the production of cytokines in CSF and serum in 16 schizophrenic patients and 10 healthy controls (tumor necrosis factor alpha - TNF alpha; interleukins IL-1 beta, IL-2, IL-6, soluble IL-2 receptor). Cytokine levels were evaluated by radioactively-labeled antibodies (IL-1 beta, IL-2, IL-6), by enzyme-linked immunoassay (TNF) and by a sandwich enzyme immunoassay (soluble IL-2 receptor). No significant differences were found in either CSF fluid or serum levels of TNF and IL-2 or IL-6. Interleukin-1 beta was significantly decreased in patients' CSF and serum as compared to controls. Soluble interleukin-2 receptor levels were decreased in CSF of patients, but highly increased in their serum in comparison with controls. Changes in various cytokine levels in CSF fluid and serum of schizophrenic patients probably reflect interrelated process of growth, degeneration or neuroimmunological abnormalities, which may all play a role in the pathophysiology of schizophrenia. The present study supports evidence for change in immune activation, probably of peripheral origin, in schizophrenic patients.
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PMID:Changes in interleukin-1 beta and soluble interleukin-2 receptor levels in CSF and serum of schizophrenic patients. 856 79

Neural cell adhesion molecule (N-CAM) is involved in cell-cell interactions during synaptogenesis, morphogenesis, and plasticity of the nervous system. Disturbances in synaptic restructuring and neural plasticity may be related to the pathogenesis of several neuropsychiatric diseases, including mood disorders and schizophrenia. Disturbances in brain cellular function may alter concentrations of N-CAM in the CSF. Soluble human N-CAM proteins are detectable in the CSF but are minor constituents of serum. We have recently found an increase in N-CAM content in the CSF of patients with schizophrenia. Although the pathogenesis of both schizophrenia and mood disorders is unknown, ventriculomegaly, decreased temporal lobe volume, and subcortical structural abnormalities have been reported for both disorders. We have therefore measured N-CAM concentrations in the CSF of patients with mood disorder. There were significant increases in amounts of N-CAM immunoreactive proteins, primarily the 120-kDa band, in the CSF of psychiatric inpatients with bipolar mood disorder type I and recurrent unipolar major depression. There were no differences in bipolar mood disorder type II patients as compared with normals. There were no significant effects of medication treatment on N-CAM concentrations. It is possible that the 120-kDa N-CAM band present in the CSF is derived from CNS cells as a secreted soluble N-CAM isoform. Our results suggest the possibility of latent state-related disturbances in N-CAM cellular function, i.e., residue from a previous episode, or abnormal N-CAM turnover in the CNS of patients with mood disorder.
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PMID:Increased neural cell adhesion molecule in the CSF of patients with mood disorder. 862 9

CSF levels of 5-hydroxyindolacetic acid (5-HIAA), the serotonin metabolite, were assayed in 10 violent and 10 matched nonviolent patients with schizophrenia. Mean group levels of 5-HIAA in cerebrospinal fluid were found to be nearly identical. Possible explanations, including effects of medications, are discussed.
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PMID:Serotonin in violent patients with schizophrenia. 877 Dec 32

Sulpiride is a substituted benzamide with a selective action on receptors of the dopamine D2-like family, and clinical and pharmacological data suggest that it could be considered to be an atypical antipsychotic. Sulpiride penetrates the blood-brain barrier poorly because of its low lipid solubility. It is mainly excreted unchanged in the urine, and accumulation of the drug could occur in patients with renal dysfunction and possibly in elderly patients with declining glomerular filtration rate. At low dosages (50 to 150 mg/day), sulpiride produces a disinhibiting and antidepressant effect, which is probably related to its action on D2 presynaptic autoreceptors, thus facilitating dopaminergic neurotransmission. Data have confirmed the efficacy of sulpiride in patients with acute or chronic schizophrenia during both short and long term treatment, but long term, placebo-controlled trials are still lacking. It is still doubtful whether sulpiride is more effective than typical antipsychotics for the treatment of negative symptoms. Data from clinical studies are controversial; the majority of authors indicate that sulpiride produces a better recovery rate from negative than from positive symptoms at low doses, but it shows a similar efficacy either on negative and positive symptoms at higher doses. The safety profile of sulpiride is similar to that of typical antipsychotics, although the frequency of adverse effects seems to be globally lower. Extrapyramidal reactions appear generally to be mild. Autonomic effects occur less frequently with sulpiride than with typical antipsychotics, showing no clinically relevant influence on cardiovascular parameters and, on the whole, good tolerability in elderly patients. Sulpiride is known to induce prolactin elevation in both serum and CSF, which may be associated with impotence in men and diminished gonadal function in women; these effects appear to be dosage-dependent. Sulpiride can be considered to be an atypical antipsychotic, considering its action on negative, defective symptoms, its partial activity against positive symptoms, and its low incidence of extrapyramidal adverse effects. Sulpiride could find its specific therapeutic role in elderly patients with schizophrenia, as it shows a good margin of safety between therapeutic dosages and toxic concentrations.
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PMID:A risk-benefit assessment of sulpiride in the treatment of schizophrenia. 880 Jun 26

Schizophrenia may result from immune or inflammatory disorders, which are mediated by cytokines. Data in this field are heterogeneous and often contradictory. We investigated circulating levels of IL-6 and TNF-alpha, two distinct proinflammatory cytokines. Using immunoassay, we assessed IL-6 and TNF-alpha in serum from chronic schizophrenic patients (n = 30) and normal controls (n = 15). Circulating levels of IL-6 were higher in patients than in controls; those of TNF-alpha were not significantly higher than in controls. In addition, IL-6 levels were higher in patients with acute exacerbation of schizophrenia than in patients with remissions. Our results suggest that immunologic abnormalities in schizophrenia may be related to a specific inflammatory process mediated by IL-6. An interesting line of research would be the evaluation of IL-6 cerebral production in CSF.
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PMID:Elevated circulating levels of IL-6 in schizophrenia. 882 53

There is increasing evidence that oxidative injury contributes to pathophysiology of schizophrenia, indicated by the increased lipid peroxidation products in plasma and CSF, and altered levels of both enzymatic and non-enzymatic antioxidants in chronic and drug-naive first-episode schizophrenic patients. The increased plasma lipid peroxidation is also supported by concomitant lower levels of esterified polyunsaturated essential fatty acids of red blood cell plasma membrane phospholipids. Because membrane phospholipids play a critical role in neuronal signal transduction, oxidative damage of these lipids may contribute to the proposed altered neurotransmitter receptor-mediated signal transduction and thereby alter information processing in schizophrenia. Adjunctive treatment with antioxidants (e.g. vitamins E and C, beta-carotene and quinones) at the initial stages of illness may prevent further oxidative injury and thereby ameliorate and prevent further possible deterioration of associated neurological and behavioral deficits in schizophrenia.
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PMID:Oxidative injury and potential use of antioxidants in schizophrenia. 888 22

Transforming growth factor (TGF)beta plays a role in injury repair in sites surrounding brain injury. The present study tested the hypothesis that TGFbeta1 and TGFbeta2 levels in the postmortem CSF of patients with neurodegenerative disorders would be elevated compared to those in normal subjects. Free TGFbeta1 and total TGFbeta2 were measured by ELISA in postmortem ventricular cerebrospinal fluid (vCSF) of patients with Parkinson's disease (n = 30), Alzheimer's disease (n = 30), multiple sclerosis (n = 15), and schizophrenia (n = 12) and of normal controls (n = 16). In addition, albumin, IgG, and total protein in vCSF were measured. Both TGFbeta1 and TGFbeta2 were significantly different between groups (P < 0.002 and P < 0.001, respectively). Parkinson's disease vCSF showed significant increases in both TGFbeta1 (P = 0.015) and TGFbeta2 (P = 0.012) compared to normal controls. There was a trend for TGFbeta2 to be elevated in Alzheimer's disease and multiple sclerosis vCSFs, which failed to achieve significance. There were no differences between controls and schizophrenics in TGFbeta1 or TGFbeta2. Alzheimer's disease vCSF showed a significant decrease in protein compared to all other groups, which was not related to blood-brain barrier permeability, age, or autolysis differences. Evidence is presented suggesting that some TGFbeta1 may leak into the vCSF from plasma. Autopsy vCSF levels of TGFbeta isoforms were found to be distinctly different from those reported for human serum, especially for TGFbeta2, which is undetectable in plasma. These results indicate that further in vivo studies of TGFbeta2 in the CSF of Parkinson's disease patients are warranted to determine the relationship between clinical status, medication, and TGFbeta2 concentrations.
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PMID:TGFbeta1 and TGFbeta2 concentrations are elevated in Parkinson's disease in ventricular cerebrospinal fluid. 893 62

Fifty patients with a DSM-III-R diagnose of schizophrenia or schizophreniform disorder were compared to 25 healthy volunteers on structural and functional brain measurements. The patients were studied during their first admission to psychiatric hospital. In the patient group correlations between structural and functional brain measurements and clinical symptoms were performed. Brain structure was studied by CT scans. The schizophrenic patients had significantly smaller brain volume and brain length and more sulcal, but not ventricular, CSF than the controls. These findings were not an effect of sex, abuse, educational status or neuroleptic treatment. Brain function was studied by rCBF measurement (at baseline conditions and during mental activation), neuropsychological tests and neurological examination. The patients had significantly lower rCBF in the prefrontal regions during baseline condition and this was more pronounced during mental activation when compared with the controls. In the striatal region the patients had higher rCBF than the controls during activation. In no other region did rCBF differ between the patients and the controls. This points to a dysfunction in schizophrenic patients somewhere in th fronto-striatal-thalamic circuit. The patients performed poorer than the controls on practically all the psychological tests. Especially poor performance was seen in the more complicated tests depending on ability of abstraction, planning and sequential organisation and on semantic memory. The patients had more neurological abnormalities than the controls. Correlations between brain structure and rCBF were few. The neurological impaired patient group had more signs of structural brain deficits than the neurological normal patient group. Poor performance on a variety of psychological tests was correlated to signs of structural cerebral deficits. The significant correlations between the neurobiological measurements and clinical symptoms in the patients were sparse. However there was a trend that more symptoms both positive, negative and thought disorder were correlated to higher rCBF values in frontal, temporal and striatal regions, and that absence of positive symptoms correlated to structural brain deficits. Thus both structural and functional brain deficits can be detected early in the disease of schizophrenia. The findings point to primary cortical deficits probably located in the frontal and temporo-limbic areas.
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PMID:Neurobiological findings in first admission patients with schizophrenia or schizophreniform disorder. 915 Oct 9

Some recent autopsy studies indicate that gamma-aminobutyric acid (GABA) function is decreased in brain areas that involve some of the well-described structural changes observed in schizophrenia. The current study examined the relationship between CSF and plasma GABA levels and brain structural measures in schizophrenia. Sixty-two drug-free, physically healthy male patients with schizophrenia (DSM-IIIR) were evaluated for plasma and CSF GABA, as well as brain structural measures on CT scans. Plasma levels of GABA were associated with prefrontal sulcal widening and VBRs, but not global sulcal widening in the schizophrenic patients. CSF GABA measures were not associated with brain structural measures, but were associated with age and age of onset. The significant relationship between plasma GABA, but not CSF GABA, and specific brain morphology measures in schizophrenic patients suggests that if GABA transmission is impaired in schizophrenia, it is a local, but not global, phenomenon.
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PMID:GABA and brain abnormalities in schizophrenia. 964 48

An impairment of the blood-cerebrospinal fluid barrier (BCB) has repeatedly been described in schizophrenic patients. A BCB impairment can be due to vascular leakage during an inflammatory process, or to neuroleptic treatment. The soluble intercellular adhesion molecule-1 (sICAM-1) has been demonstrated to be a reliable marker for an inflammatory process causing an BCB impairment. To clarify the basis of a BCB impairment in schizophrenic patients, we measured the sICAM-1 levels in CSF of 40 schizophrenic patients. High concentrations of sICAM-1 were found to be related to high concentrations of albumin, IgG and total protein in CSF. A BCB impairment was associated with high levels of sICAM-1. Our data indicate an inflammatory mechanism of BCB impairment in schizophrenics and should enrich the discussion on an expanded immunological diagnosis in schizophrenia.
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PMID:Blood-cerebrospinal fluid barrier impairment as indicator for an immune process in schizophrenia. 979 46


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