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

The objective of this study was to determine whether sequence variation in the tumor necrosis factor alpha (TNF alpha) gene is associated with MS course and severity in Olmsted County, MN. The severity and temporal course of MS are heterogeneous. Genetic factors may play a role in determining the course of MS. TNF alpha expression is temporally associated with exacerbations of MS and is increased in individuals with progressive disease. The entire TNF alpha gene was amplified by polymerase chain reaction in 78 MS patients and in 39 patients with schizophrenia. Denaturation finger-printing, a modification of direct sequencing that detects virtually all genetic polymorphisms, was performed for four regions spanning the functionally significant portions of the gene, including the promoter region. Polymorphisms were confirmed by complete sequencing. The severity and temporal course of MS were compared in those with wild-type versus variant alleles. Four sequence changes were detected, three of which occurred in MS patients. None occurred in a protein-encoding sequence. Neither of the two most common sequence variants were associated with disease severity or temporal course. Genetic variation of the TNF alpha gene is not associated with variation in the course or long-term outcome of MS in this population-based sample.
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PMID:Genetic variation in the tumor necrosis factor alpha gene and the outcome of multiple sclerosis. 927 May 65

Dysregulation of the inflammatory response system has been linked to pathophysiology of schizophrenia. Evidence of immune activation has derived from the detection of abnormal levels of proinflammatory cytokines and their receptors in peripheral blood and cerebrospinal fluid from schizophrenic patients. Cytokines are involved in normal CNS development as well as in the pathogenesis of many neuro-psychiatric disorders, acting directly on neural cells or modulating neurotransmitter and neuropeptide systems. In particular tumor necrosis factor alpha (TNFalpha), depending on its concentration, can exert both neurotrophic and neurotoxic effects and influence neural cell growth and proliferation. Moreover, TNFalpha gene is located on the small arm of chromosome 6 (6p21.1-21.3), a locus associated with genetic susceptibility to schizophrenia. We studied the distribution of -G308A TNFalpha gene polymorphism in 84 schizophrenic patients and in 138 healthy volunteers. This biallelic base exchange polymorphism directly affects TNFalpha plasma levels. Frequency of the TNF2(A) allele is significantly increased in schizophrenic patients as compared to controls (P = 0.0042). Genotype distribution is also significantly different (P = 0.0024). TNF2 homozygotes are represented only in the patient group (P = 0.002). These data suggest a potential role of TNFalpha as a candidate gene for susceptibility to schizophrenia and suggest that immune dysregulation in schizophrenic patients could also have a genetic component.
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PMID:Association between -G308A tumor necrosis factor alpha gene polymorphism and schizophrenia. 1288

Atypical antipsychotics such as clozapine represent a significant improvement over typical antipsychotics in the treatment of schizophrenia, particularly regarding extrapyramidal symptoms. Despite their benefits, use is limited by the occurrence of adverse reactions such as sedation and weight gain. This article provides a comprehensive review and discussion of obesity-related pathways and integrates these with the known mechanisms of atypical antipsychotic action to identify candidate molecules that may be disrupted during antipsychotic treatment. Novel preliminary data are presented to genetically dissect these obesity pathways and elucidate the genetic contribution of these candidate molecules to clozapine-induced weight gain. There is considerable variability among individuals with respect to the ability of clozapine to induce weight gain. Genetic predisposition to clozapine-induced weight gain has been suggested. Therefore, genetic variation in these candidate molecules may predict patient susceptibility to clozapine-induced weight gain. This hypothesis was tested for 10 genetic polymorphisms across 9 candidate genes, including the serotonin 2C, 2A, and 1A receptor genes (HTR2C/2A/1A); the histamine H1 and H2 receptor genes (H1R/H2R); the cytochrome P450 1A2 gene (CYPIA2); the beta3 and alpha,alpha-adrenergic receptor genes (ADRB3/ADRAIA); and tumor necrosis factor alpha (TNF-alpha). Prospective weight gain data were obtained for 80 patients with schizophrenia who completed a structured clozapine trial. Trends were observed for ADRB3, ADRA1A, TNF-alpha, and HTR2C; however, replication in larger, independent samples is required. Although in its infancy, psychiatric pharmacogenetics will in the future aid clinical practice in the prediction of response and side effects, such as antipsychotic-induced weight gain, and minimize the current "trial and error" approach to prescribing.
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PMID:Genetic dissection of atypical antipsychotic-induced weight gain: novel preliminary data on the pharmacogenetic puzzle. 1160 85

We investigated levels of maternal cytokines in late pregnancy in relation to the subsequent development of adult schizophrenia and other psychoses in their offspring. The sample included the mothers of 27 adults with schizophrenia and other psychotic illnesses and 50 matched unaffected controls from the Providence cohort of the Collaborative Perinatal Project. Serum samples were analyzed for interleukin 1 beta (IL-1-beta), interleukin 2 (IL-2), interleukin 6 (IL-6), interleukin 8 (IL-8), and tumor necrosis factor alpha (TNF-alpha) by enzyme immunoassay. Maternal levels of TNF-alpha were significantly elevated among the case series (t = 2.22, p =.04), with evidence of increasing odds of psychosis in relation to higher cytokine levels. We did not find significant differences between case and control mothers in the serum levels of IL-1, IL-2, IL-6, or IL-8. These data support previous clinical investigations reporting maternal infections during pregnancy as a potential risk factor for psychotic illness among offspring.
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PMID:Maternal cytokine levels during pregnancy and adult psychosis. 1178 7

There is some evidence that the pathophysiology of schizophrenia is related to changes in the innate and adaptive immune systems. In an attempt to define a potential immunological dysfunction in schizophrenia, we measured the serum levels of several cytokines in the sera of 24 patients with paranoid schizophrenia and investigated the cytokine production in whole blood assays after stimulation in vitro with virus (Newcastle disease), phytohemagglutinin (PHA) or bacterial lipopolysaccharide (LPS) and compared them with healthy, normal controls. A significant increase of interleukin 6 (IL-6), IL-8 and interferon gamma (IFN-gamma) levels, but a decreased L-10 level were observed in the sera of patients with schizophrenia. No significant changes in the serum levels of IL-2, IL-4, IFN-alpha and tumor necrosis factor alpha (TNF-alpha) were detected in these patients. When cytokine production in vitro was examined, a significant defect in PHA-induced IL-2, L-4 and IFN-gamma, and in virus-induced IFN-alpha production, but no significant alterations in LPS-induced IL-6, IL- 10 and TNF-alpha production were observed. In summary, increased serum levels of some cytokines such as IL-6, IL-8 and IFN-gamma indicate an activation of the inflammatory response in schizophrenia, while the in vitro assay indicates significant changes in the Th1 (decreased production of 1L-2 and IFN-gamma) and Th2 (decreased production of IL-4) cell system responses. The role of the defective EFN-alpha production in the regulation of the imbalance between Th1 and Th2 cell system responses is suggested.
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PMID:Investigation of serum cytokine levels and cytokine production in whole blood cultures of paranoid schizophrenic patients. 1181 38

The purpose of the present study was to examine the association between the tumor necrosis factor (TNF)-alpha gene (A) polymorphism and schizophrenia in a Korean sample of schizophrenic patients and control subjects. Genotyping for the TNFA polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism. Genotype and allele distributions of the TNFA polymorphism between schizophrenic patients and controls were not significantly different. In the light of these results, the TNFA polymorphism seems not to confer susceptibility to the pathogenesis of schizophrenia, at least in the Korean population.
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PMID:Tumor necrosis factor-alpha gene polymorphism at position -308 and schizophrenia in the Korean population. 1283 21

Two research groups have thus far reported a significant association between schizophrenia and a promoter polymorphism (-308G > A) of the gene encoding tumor necrosis factor alpha (TNF-alpha), while contradictive negative results have also been reported. We examined the possible association in a Japanese sample of 297 schizophrenia cases and 458 controls. Allele frequencies of both the patients and controls were very low (1.5% and 0.8%, respectively), and the difference was not statistically significant. We conclude that the effect of the -308G > A polymorphism on the development of schizophrenia is, if any, weak and the majority of Japanese schizophrenics are unrelated to the -308G > A polymorphism of the TNF-alpha gene.
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PMID:Association analysis of the -308G>A promoter polymorphism of the tumor necrosis factor alpha (TNF-alpha) gene in Japanese patients with schizophrenia. 1476 24

An increasing amount of evidence suggests that the pathophysiology of schizophrenia is associated with activation of the immune system. Four studies have established an association of -308G/A polymorphism of tumor necrosis factor alpha (TNF-alpha), a cytokine involved in inflammatory processes, with schizophrenia [Mol. Psychiatry 6 (2001) 79; Mol. Psychiatry 8 (2003) 718; Schizophr. Res. 65 (2003) 19; Biol. Psychiatry 54 (2003) 1205]. In the present study, however, no significant positive association has been found between any individual SNP or haplotype constituted of the five promoter polymorphisms (-1031T/C, -863C/A, -857C/T, -308G/A and -238G/A) in the human TNF-alpha gene and schizophrenia (314 Chinese Han schizophrenic patients and 340 healthy control). A meta-analysis we did in this work, which is based on previous nine studies plus our own unpublished data including a total of 2399 schizophrenic patients (sporadic cases 2099, familial cases >505) and more than 3261 controls, failed to show significant difference of -308G/A distribution between patients and controls in both the whole sample and the pooled Asian sample. By contraries, the significant results in the pooled Caucasian sample imply an ethnic heterogeneity in -308G/A variation in the TNF-alpha gene in schizophrenia.
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PMID:No association between the promoter variants of tumor necrosis factor alpha (TNF-alpha) and schizophrenia in Chinese Han population. 1527 34

Using restriction fragment length polymorphism and pyrosequencing methods, we genotyped two TNFA gene promoter SNPs (-G308A, -G238A) and analyzed the haplotype structure in 24 Canadian families of primarily Celtic origin. Our results demonstrate that after correction for multiple testing based on simulations of 10 000 replicates of unlinked/unassociated data, there is evidence for association (P=0.026) of a specific haplotype (-308A, -238G) with schizophrenia and schizophrenia spectrum disorders with a family-based trimmed haplotype linkage disequilibrium test (Trimhap). Stratifying the 22 families with genome scan data by TNFA promoter haplotypes followed by reanalysis of linkage to schizophrenia throughout the genome, we identified few loci that exhibit a considerable increase in LOD/HLOD scores. A locus on chromosome 1q44 (D1S1609) demonstrated a significant increase (P=0.025) in LOD score from 0.15 to 3.01 with a broad definition of the schizophrenia phenotype and a dominant mode of inheritance. This result replicates a previously reported positive result of linkage of schizophrenia spectrum disorders to this area of the genome. We also illustrated that simulation studies are pivotal in evaluating the significance of results obtained with newer statistical methods, when multiple, but not independent, tests are performed, and when sample stratification is utilized to reduce the impact of heterogeneity or assess the interaction between loci.
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PMID:Tumor necrosis factor promoter haplotype associated with schizophrenia reveals a linked locus on 1q44. 1534 Mar 54


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