UMLS:C0036341 - FACTA Search

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 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

A single nucleotide polymorphism (TNF(-308A)) within the promoter region of the gene encoding tumor necrosis factor (TNF), has been significantly associated with schizophrenia in a study of Italian patients and control subjects Boin et al. [2001: Mol Psychiatry 6:79-82]. We have applied case-control analyses to examine TNF promoter haplotypes (containing TNF(-308) and two additional promoter variants: TNF(-376) and TNF(-238)) in four schizophrenia cohorts drawn from Australian, Indian Fijian, Indigenous Fijian, and Brahmin populations. In addition, we have applied the sibling transmission disequilibrium (STD) test to promoter haplotypes within 81 trios drawn from Australian Caucasian pedigrees with multiple schizophrenia cases, and 86 trios drawn from the Brahmin population of Tamil Nadu province in Southern India. Within each of these cohorts, we found no evidence of recombination between these tightly linked promoter variants, supporting previous studies which demonstrated that only a subset of the eight possible haplotypes exist. Of the four observed haplotypes, we and others have observed only one carries the TNF(-308A) variant allele. We report no significant differences in TNF promoter haplotype frequencies between the patient and control groups within each population, although the Indian Fijian cohort showed a trend towards reduced TNF(-308A) alleles amongst schizophrenia cases (P = 0.07). We found no evidence of bias in TNF promoter haplotype transmission to schizophrenia probands. Very similar results were obtained when only the TNF(-308) polymorphism was considered. Taken together, these data provide no support for the involvement of TNF promoter variants TNF(-308), TNF(-376), and TNF(-238) in schizophrenia susceptibility within four ethnically distinct cohorts.
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PMID:Tumor necrosis factor haplotype analysis amongst schizophrenia probands from four distinct populations in the Asia-Pacific region. 1289 67

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

Experimental findings from psychoimmunologic research in humans and epidemiological data suggest that alterations in cytokine networks may induce acute psychopathologic symptoms and may be involved in the pathogenesis and pathophysiology of schizophrenia by influencing brain development. However, there is insufficient evidence from genetic, post-mortem, and cerebrospinal fluid studies to demonstrate this in the CNS of schizophrenic patients. In contrast, there are quite robust findings from peripheral blood that interleukin (IL)-2, IL-6, tumor necrosis factor-alpha, and interferon cytokine systems in patients are regulated differently than in controls. However, these findings are not specific to schizophrenia, they are confounded by numerous intervening variables such as stress, smoking, and medication, and their pathophysiologic relevance for processes in the CNS is undetermined. Therefore, future research on the involvement of cytokines in the pathogenetics, pathophysiology, and treatment of schizophrenia is needed.
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PMID:[Cytokine network in patients with schizophrenia and its significance for the pathophysiology of the illness]. 1502 22

Prenatal exposure to infection increases risk for schizophrenia, and we have hypothesized that inflammatory cytokines, generated in response to maternal infection, alter neuron development and increase risk for schizophrenia. We sought to study the effect of cytokines generated in response to infection-interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNFalpha), and interleukin-6 (IL-6)-on the dendritic development of cortical neurons. Primary mixed neuronal cultures were obtained from E18 rats and exposed to 0, 100, or 1000 units (U)/ml of IL-1beta, TNFalpha, IL-6, or IL-1beta+TNFalpha for 44 h. MAP-2-positive neurons were randomly identified for each condition and the number of primary dendrites, nodes, and total dendrite length was determined. We found that 100 U of TNFalpha significantly reduced the number of nodes (27%, p=0.02) and total dendritic length (14%, p=0.04), but did not affect overall neuron survival. A measure of 100 U IL-1beta+TNFalpha significantly reduced the number of primary dendrites (17%, p=0.006), nodes (32%, p=0.001), and total dendritic length (30%, p<0.0001), although it did not affect overall neuron survival. At 1000 U, each cytokine significantly reduced the number of primary dendrites (14-24%), nodes (28-37%), as well as total dendritic length (25-30%); neuron survival was reduced by 14-21%. These results indicate that inflammatory cytokines can significantly reduce dendrite development and complexity of developing cortical neurons, consistent with the neuropathology of schizophrenia. These findings also support the hypothesis that cytokines play a key mechanistic role in the link between prenatal exposure to infection and risk for schizophrenia.
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PMID:Prenatal infection and risk for schizophrenia: IL-1beta, IL-6, and TNFalpha inhibit cortical neuron dendrite development. 1508 88

Both omega-6 and omega-3 long-chain polyunsaturated fatty acids (LCPUFAs) modulate TH1 and TH2 cell generation, their cytokine production, and cell proliferation and thus may serve as endogenous anti-inflammatory molecules. LCPUFAs suppress the production of tumor necrosis factor-alpha (TNF-alpha) (and so also of OX40, since it belongs to the family of TNFR) and the expression of Bcl-2, suggesting that these fatty acids have the ability to prevent/suppress autoimmune diseases. Human breast milk contains substantial amounts of both omega-3 and omega-6 fatty acids. This indicates that LCPUFAs present in human breast milk suppress the levels of OX40 and decrease the expression of Bcl-xL and Bcl-2 on exposure to self-antigens and thus, protects against the development of autoimmune diseases in later life. In view of this, I propose that supplementation of appropriate amounts of LCPUFAs during perinatal period protects against atopy, asthma, auto-immune diseases, type 1 and type 2 diabetes mellitus, hypertension, coronary heart disease, metabolic syndrome X, lymphomas, leukemias and other cancers, schizophrenia, depression and other adult diseases in which low-grade systemic inflammation plays a significant role. It is also likely that perinatal supplementation of LCPUFAs in adequate amounts modulates the expression of genes concerned with immune response, angiogenesis, central osmo/sodium and glucose sensors etc. This renders various tissues and organs including T cells and macrophages, endothelial cells, hypothalamic neurons, and various cardiovascular tissues to be able to counteract the pathological mechanisms that tend to induce various adult diseases by blunting the inflammatory responses in those who received adequate amounts of LCPUFAs during the perinatal period compared to those who did not.
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PMID:Perinatal supplementation of long-chain polyunsaturated fatty acids, immune response and adult diseases. 1511 76

The study population comprised 94 Finnish patients with DSM-IV diagnosis of schizophrenia. The patients were placed into two subgroups according to medication response to conventional neuroleptics. The aim of the study was to examine the frequency of tumor necrosis factor -308 (G > A) polymorphism in these patients and their 98 control subjects who were age- and gender-matched blood donors. Associations between TNFalpha -308 polymorphism alone and between the interaction of TNFalpha and epidermal growth factor gene polymorphisms, and medication response and age at onset of schizophrenia were also studied. The frequencies of TNFalpha A-allele were 11.7 % in patients and 12.8% in controls. The difference was not significant (p = 0.75). TNFalpha -308 polymorphism was not associated with medication response. However, patients with EGF AA and TNFalpha AG/AA genotype had a lower age at onset of schizophrenia compared with the rest of the patients not having this combination (20.0 years, 3.3 vs. 30.2 years, 10.1 mean + SD; p < 0.001). The results support earlier findings according to which TNFalpha polymorphism is not associated with the incidence of schizophrenia. On the other hand, the role of cytokines in schizophrenia may involve genetic interactions predisposing early onset of illness.
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PMID:Interaction of tumor necrosis alpha - G308A and epidermal growth factor gene polymorphisms in early-onset schizophrenia. 1561 91

This study investigated the potential interaction between the polymorphisms of serotonin transporter gene (SLC6A4, a 44 base pair insertion/deletion in the promoter region, 5-HTTLPR) and tumor necrosis factor-alpha gene (TNFA; -238G/A and -308G/A polymorphisms) on the development of schizophrenia, as well as the interaction of the three polymorphisms in relation to symptomatology, family history, onset age and antipsychotic treatment response. Genomic DNA analyses with polymerase chain reaction (PCR) was used for the genotyping. One hundred and fifty-two (152) patients with schizophrenia and 152 normal controls participated in the study. Any associations between the individual polymorphism and schizophrenia were not found. However, marginal association between subjects with both TNFA -238 A allele (genotype AA plus AG) and 5-HTTLPR s allele (ss plus sl) and presence of family history was found (p = 0.023; p = 0.026). The subjects with TNFA -308 AG genotype showed higher change in PANSS total score (p = 0.028). No significant interaction effect between 5-HTTLPR and TNFA -238/-308 polymorphisms either on the development of schizophrenia or on antipsychotics treatment response and psychopathology was found, although a significant interaction effect for subjects carrying TNFA -238 AG and -308 AA genotypes on a positive family history was observed (p = 0.017). These results suggest that the interaction effects between 5-HTTLPR and TNFA -238/-308 polymorphisms gives no significant contribution to the susceptibility to schizophrenia, and is not associated with clinical variables, antipsychotic treatment response and psychopathological features, except for family history of disease, at least in the Korean population.
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PMID:Interaction analysis between 5-HTTLPR and TNFA -238/-308 polymorphisms in schizophrenia. 1625 73

Maternal infection during pregnancy is associated with a higher incidence of mental disorders, including schizophrenia, in the offspring in later life. Our recent attempt to study this link between prenatal immunological challenge and subsequent psychopathology has led to the establishment of a mouse model demonstrating the emergence of multiple psychotic-like phenotypes following immunological challenge on gestation day (GD) 9. However, little is known about the impact of similar in utero challenge at different times of pregnancy. Here, we compare the efficacy of identical maternal immune stimulation induced by the exposure to polyriboinosinic-polyribocytidilic acid (Poly(I:C)) at a dose of 5mg/kg (i.v.) on distinct days of gestation (GD 6, 9, 13 or 17). The offspring derived were then compared to those collected from vehicle- and non-treated dams in two paradigms of selective associative learning: latent inhibition (LI) and the US-pre-exposure effect (USPEE). LI deficiency was observed in animals born to dams treated with Poly(I:C) on GD 6, 9 or 13, but not in those on GD17. In contrast, a loss of the USPEE was equivalently seen in all Poly(I:C) treatment groups, regardless of treatment times. Evaluation of the acute cytokine response in a separate cohort of pregnant dams receiving Poly(I:C) challenge on either GD9 or GD17 revealed that the ratio of interleukin-10/tumor necrosis factor-alpha was elevated in the GD17 relative to the GD9 group. The present report thus provides evidence that the acute cytokine reaction as well as the long-term pattern of behavioural sequelae of maternal immune challenge can be affected by its precise timing during pregnancy. The present study provides further support to the use of the prenatal Poly(I:C) model in the elucidation of mechanisms involved in the aetiology and disease process of immuno-precipitated neurodevelopmental mental diseases, including but not limited to, schizophrenia.
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PMID:Immunological stress at the maternal-foetal interface: a link between neurodevelopment and adult psychopathology. 1637 11

Weight gain is associated with the use of many psychotropic medications, including antidepressants, mood stabilizers, antipsychotic drugs, and may have serious long term consequences: it can increase health risks, specifically from overweight (BMI = 25-29.9 kg/m2) to obesity (BMI > or =30 kg/m2), according to Body Mass Index (BMI), and the morbidity associated therewith in a substantial part of patients (hypertension, coronary heart desease, ischemic stroke, impaired glucose tolerance, diabetes mellitus, dyslipidemia, respiratory problems, osteoarthritis, cancer); according to patients, psychosocial consequences such as a sense of demoralization, physical discomfort and being the target of substantial social stigma are so intolerable that they may discontinue the treatment even if it is effective. The paper reviews actual epidemiological data concerning drug induced weight gain and associated health problems in psychiatric patients : there is a high risk of overweight, obesity, impaired glucose tolerance, diabetes mellitus, premature death, in patients with schizophrenia or bipolar disorder; and the effects of specific drugs on body weight: Tricyclic Antidepressants (TCA) induced weight gain correlated positively with dosage and duration of treatment, more pronounced with amitriptyline ; Selective Serotonin Reuptake Inhibitors (SSRI) decrease transiently bodyweight during the first few weeks of treatment and may then increase bodyweight; weight gain appears to be most prominent with some mood stabilizers (lithium, valproate); atypical antipsychotics tend to cause more weight gain than conventional ones and weight gain, diabetes, dyslipidemia, seem to be most severe with clozapine and olanzapine. Conceming the underlying mechanisms of drug induced weight gain, medications might interfere with central nervous functions regulating energy balance; patients report about: increase of appetite for sweet and fatty foods or "food craving" (antidepressants, mood stabilizers, antipsychotic drugs) and weight gain despite reduced appetite which can be explained by an altered resting metabolic rate (TCA, SSRI, Monoaminoxidase Inhibitors MAO I). According to current concepts, appetite and feeding are regulated by a complex of neurotransmitters, neuromodulators, cytokines and hormones interacting with the hypothalamus, including the leptin and the tumor necrosis factor system. The pharmacologic mechanisms underlying weight gain are presently poorly understood: maybe the different activities at some receptor systems may induce it, but also genetic predisposition. Understanding of the metabolic consequences of psychotropic drugs (weight gain, diabetes, dyslipidemia) is essential: the insulin-like effect of lithium is known; treatment with antipsychotic medications increases the risk of impaired glucose tolerance and diabetes mellitus. Several management options of weight gain are available from choosing or switching to another drug, dietary advices, increasing physical activities, behavioural treatment, but the best approach seems to attempt to prevent the weight gain : patients beginning maintenance therapy should be informed of that risk, and nutritional assessment and counselling should be a routine part of treatment management, associated with monitoring of weight, BMI, blood pressure, biological parameters (baseline and three months monitoring of fasting glucose level, fasting cholesterol and triglyceride levels, glycosylated haemoglobin). Psychiatrics must pay attention to concomitant medications and individual factors underlying overweight and obesity. Weight gain has been described since the discovery and the use of the firstpsychotropic drugs, but seems to intensify with especially some of the second generation antipsychotic medications ; understanding of the side effects of psychotropic drugs, including their metabolic consequences (weight gain, diabetes, dyslipidemia) is essential for the psychiatrics to avoid on the one hand a risk of lack of compliance, a discontinuation of the pharmacological medication and also a risk of relapse and rehospitalization, and on the other hand to avoid acute life threatening events (diabetic ketoacidocetosis and non ketotic hyperosmolar coma, long term risk complications of diabetes and overweight).
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PMID:[Psychotropic drugs induced weight gain: a review of the literature concerning epidemiological data, mechanisms and management]. 1638 18

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