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 line of evidence indicates changes of the immune system in schizophrenic patients. We investigated the production of cytokines by peripheral blood mononuclear cells (PBMCs) in drug-free and neuroleptic-treated schizophrenic patients compared to healthy, normal controls. A significant reduction in interleukin (IL)-2 production was detected in untreated schizophrenic patients (-59.6%; p < .05) as well as in IL-3-like activity (IL-3-LA) production (-27.4%; p < .05) in treated patients compared to controls. No alteration was observed in IL-1 beta production. It seems that schizophrenia is associated with diminished IL-2 production, while neuroleptic treatment interferes with the capacity of immunocompetent cells to synthesize and/or release Il-3-LA. The alteration in cytokine production did not correlate with either the severity of the disorder or the serum prolactin levels.
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PMID:Cytokine production in drug-free and neuroleptic-treated schizophrenic patients. 749 23

This study was carried out to examine some components of in vivo immune function in major depression and schizophrenia. Toward this end, plasma concentrations of interleukin-1 beta (IL-1 beta) and IL-6, soluble IL-2 receptor (sIL-2R), and transferrin receptor (TfR) were measured in 28 normal controls, 11 schizophrenics and 13 major-depressed patients. Schizophrenic and major-depressed patients showed significantly higher plasma sIL-2R and TfR than normal controls. There was a trend toward higher plasma IL-6 in the psychiatric patients, and particularly in schizophrenic patients, than in normal volunteers. In normal controls and in the total study group, there were highly significant and positive correlations between plasma TfR and sIL-2R concentrations. It is suggested that schizophrenia and major depression are characterized by immune disorders that may indicate activation of cell-mediated immunity such as T-cell activation.
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PMID:Plasma-soluble interleukin-2 and transferrin receptor in schizophrenia and major depression. 777 17

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

Pro-inflammatory cytokines are dysregulated in schizophrenia. To determine the nature of the so-called inflammatory syndrome in schizophrenia, we investigated the circulating levels of various cytokines (interleukin (IL)-1 beta, IL-6, tumor necrosis factor (TNF)alpha), their natural antagonist (IL1-ra, TNF-RI, TNF-RII) and leukocyte activation markers (the soluble receptor of interleukin-2, soluble CD14 and soluble CD23) in subjects with chronic schizophrenia (n = 18) and in normal controls (n = 21). The levels of IL-1 beta and its antagonist and the levels of leukocyte activation markers were not significantly differents between patients and controls. Circulating levels of TNF alpha were significantly (p < 0.05) higher in patients than in controls and did not result from variations of its antagonist levels. The significant (p < 0.05) increase in patient IL-6 was related specifically to clinical status, i.e. illness duration. These data suggest a specific cytokine-mediated syndrome in schizophrenia. We hypothesize that TNF alpha and IL-6 reflect the genetic background of disease suceptibility.
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PMID:A differential role for interleukin-6 and tumor necrosis factor-alpha in schizophrenia? 932 55

Perinatal infections are a risk factor for fetal neurological pathologies, including cerebral palsy and schizophrenia. Cytokines that are produced as part of the inflammatory response are proposed to partially mediate the neurological injury. This study investigated the effects of intraperitoneal injections of lipopolysaccharide (LPS) to pregnant rats on the production of cytokines and stress markers in the fetal environment. Gestation day 18 pregnant rats were treated with LPS (100 microg/kg body wt i.p.), and maternal serum, amniotic fluid, placenta, chorioamnion, and fetal brain were harvested at 1, 6, 12, and 24 h posttreatment to assay for LPS-induced changes in cytokine protein (ELISA) and mRNA (real-time RT-PCR) levels. We observed induction of proinflammatory cytokines interleukin (IL)-1 beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha) as well as the anti-inflammatory cytokine IL-10 in the maternal serum within 6 h of LPS exposure. Similarly, proinflammatory cytokines were induced in the amniotic fluid in response to LPS; however, no significant induction of IL-10 was observed in the amniotic fluid. LPS-induced mRNA changes included upregulation of the stress-related peptide corticotropin-releasing factor in the fetal whole brain, TNF-alpha, IL-6, and IL-10 in the chorioamnion, and TNF-alpha, IL-1 beta, and IL-6 in the placenta. These findings suggest that maternal infections may lead to an unbalanced inflammatory reaction in the fetal environment that activates the fetal stress axis.
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PMID:Maternal LPS induces cytokines in the amniotic fluid and corticotropin releasing hormone in the fetal rat brain. 1498 88

Interleukines (IL) levels, mononuclear phagocytes (MP) activity and proliferative T-lymphocytes activity were studied in 6 patients with paranoid (ICD-10 item F20.00) and 20 patients with shift-like (F20.01) types of schizophrenia. Significant (p < 0.05) decrease of MP activity, monocytes-stimulated IL-1 beta production (mostly pronounced in paranoid type) lymphocyte-stimulated IL-2 production (p < 0.05) and proliferate T-lymphocytes activity (p < 0.01) were characteristic of schizophrenia in use of low mitogen doses. A significant increase (p < 0.001) of IL-2 serum concentration was found only in shift-like type. The changes of IL-2 concentration are more frequent in younger patients, aged up to 30 years, with relatively long duration of illness and manifestation stage (over 5 years). An increase of serum IL-2 in the patients was not connected with the changes of soluble IL-2 receptors in the serum as it did not differ from the control values.
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PMID:[Interleukin system in schizophrenics]. 1500 20

Hypoactivity of the dorsolateral prefrontal cortex (DLPFC) during cognitive tasks is among the most consistent findings in schizophrenia. The biological factors contributing to this hypofrontality are only partially known. Previous reports have shown the influence of genes mapped to IL-1 cluster (i) in the risk to develop schizophrenia and (ii) on brain morphological abnormalities in these patients. Moreover, Interleukin-1beta (IL-1beta), encoded by IL-1B gene (IL-1 cluster, chromosome 2q13) has a key role in dopaminergic differentiation and dendrite growth in developing cortical neurons. The authors explored the role of a genetic functional polymorphism at IL-1B gene in relation to DLPFC activity. DLPFC (left and right) metabolic activity was measured in a sample of 19 DSM-IV diagnosed schizophrenic patients of Spanish origin using a procedure based on MRI/PET image fusion. During PET studies, subjects performed a contingent Continuous Performance Test aiming to activate DLPFC. Functional promoter polymorphism -511 C/T (rs16944) of IL-1B gene was genotyped in these patients. Those patients who were allele 2 (-511 T) carriers showed a lower metabolic activity in the left DLPFC with respect to patients homozygous for allele 1 (-511 C) (U = 16, z = -2.32, P = 0.02). Our results suggest that hypofrontality reported in some schizophrenic patients might be explained, at least in part, by this functional polymorphism at IL-1B gene. Genetic variants with influence on brain functionality may account for the neurocognitive heterogeneity observed in schizophrenic patients.
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PMID:Effect of interleukin-1beta gene functional polymorphism on dorsolateral prefrontal cortex activity in schizophrenic patients. 1751 Sep 51

Genetic factors have a variable impact on Alzheimer's Disease (AD), ranging from familial forms that are transmitted in an autosomal dominant fashion to sporadic AD, where a polygenic component is present. Most genes conferring susceptibility to AD are related to amyloid-beta deposition (APP; PS1; PS2; APOE; Cystatin-C; ubiquilin-1), oxidative stress (NOS2; NOS3) and inflammatory response (IL-1 alpha; IL-1 beta; IL-6; TNF-alpha). Genome-wide analyses, transcriptomics and proteomics approaches have pointed also to proapoptotic genes as increasing AD liability. Depression and psychotic symptoms that occur in a large proportion of AD patients have been associated with monoamine genes coding for metabolic enzymes (COMT), transporters (5-HTTLPR) and receptors (DRD1; DRD3). Genetic testing may be useful to confirm the diagnosis of AD in individuals with clinical signs of dementia, while it is generally not recommended as a predictive testing for AD in asymptomatic individuals. Drugs currently in use to treat AD are effective in only 20% of patients; their therapeutic effect is predominantly under genetic control (CYP26 gene; APOE). Environmental factors have been shown to moderate the effects of genes on psychiatric disorders such as depression, schizophrenia and ADHD. The study of gene-environment interactions in AD, that are still poorly understood, is essential to predict disease-risk in asymptomatic individuals. Genomics will provide a dynamic picture of biological processes in AD and new targets for the forthcoming anti-AD drugs.
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PMID:Genetics of Alzheimer's disease. A rapidly evolving field. 1785 Nov 96

Schizophrenia is a complex disorder, where family, twin and adoption studies have been demonstrating a high heritability of the disease and that this disease is not simply defined by several major genes but rather evolves from addition or potentiation of a specific cluster of genes, which subsequently determines the genetic vulnerability of an individual. Linkage and association studies suggest that a genetic vulnerablility, is not forcefully leading to the disease since triggering factors and environmental influences, i.e. birth complications, drug abuse, urban background or time of birth have been identified. This has lead to the assumption that schizophrenia is not only a genetically defined static disorder but a dynamic process leading to dysregulation of multiple pathways. There are several different hypothesis based on several facets of the disease, some of them due to the relatively well-known mechanisms of therapeutic agents. The most widely considered neurodevelopmental hypothesis of schizophrenia integrates environmental influences and causative genes. The dopamine hypothesis of schizophrenia is based on the fact that all common treatments involve antidopaminergic mechanisms and genes such as DRD2, DRD3, DARPP-32, BDNF or COMT are closely related to dopaminergic system functioning. The glutamatergic hypothesis of schizophrenia lead recently to a first successful mGlu2/3 receptor agonistic drug and is underpinned by significant findings in genes regulating the glutamatergic system (SLC1A6, SLC1A2 GRIN1, GRIN2A, GRIA1, NRG1, ErbB4, DTNBP1, DAAO, G72/30, GRM3). Correspondingly, GABA has been proposed to modulate the pathophysiology of the disease which is represented by the involvement of genes like GABRA1, GABRP, GABRA6 and Reelin. Moreover, several genes implicating immune, signaling and networking deficits have been reported to be involved in the disease, i.e. DISC1, RGS4, PRODH, DGCR6, ZDHHC8, DGCR2, Akt, CREB, IL-1B, IL-1RN, IL-10, IL-1B. However, molecular findings suggest that a complex interplay between receptors, kinases, proteins and hormones is involved in schizophrenia. In a unifying hypothesis, different cascades merge into another that ultimately lead to the development of symptoms adherent to schizophrenic disorders.
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PMID:Molecular mechanisms of schizophrenia. 1798 52

Twin, family and recent molecular studies support the hypothesis of genetic overlapping between schizophrenia and bipolar disorder. Brain structural features shared by both psychiatric disorders might be the phenotypic expression of a common genetic risk background. Interleukin-1 (IL-1) cluster (chromosome 2q13) genetic variability, previously associated with an increased risk both for schizophrenia and for bipolar disorder, has been also associated with gray matter (GM) deficits, ventricular enlargement and hypoactivity of prefrontal cortex in schizophrenia. The aim of the present study was to analyze the influence of IL-1 cluster on brain morphology in bipolar disorder. Genetic variability at IL-1B and IL-1RN genes was analyzed in 20 DSM-IV (Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition) bipolar patients. Magnetic resonance imaging (MRI) measurements were obtained for whole-brain GM and white matter, dorsolateral prefrontal cortex (DLPFC), superior temporal gyrus, hippocampus and lateral ventricles. MRI data were corrected for age and cranial size using regression parameters from a group of 45 healthy subjects. A -511C/T polymorphism (rs16944) of IL-1B gene was associated with whole-brain GM deficits (P = 0.031) and left DLPFCGM deficits (P = 0.047) in bipolar disorder patients. These findings support the hypothesis of IL-1 cluster variability as a shared genetic risk factor contributing to GM deficits both in bipolar disorder and in schizophrenia. Independent replication in larger samples would be of interest to confirm these results.
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PMID:Gray matter deficits in bipolar disorder are associated with genetic variability at interleukin-1 beta gene (2q13). 1912 64


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