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)

Interleukin (IL)-6 mediates brain-immune interactions, influences the survival of postnatal mesencephalic and basal forebrain cells, influences mesocorticolimbic dopamine and serotonin neurotransmission, and is linked with various central nervous system disorders. In the present study, single injections of IL-6 (1 or 2 microg/Long-Evans rat, i.p.) induced modest elevations of locomotor activity. The locomotor increases were not augmented by repeated intermittent injections of IL-6 (five daily injections; 1 microg/rat), however. Nonetheless, repeated IL-6 treatment increased sensitivity to the locomotor-stimulating effects of 1.0 and 0.5 mg/kg amphetamine, when tested 5, 7, or 14 days following interruption of the cytokine treatment. The ability of acute IL-6 injections to alter locomotor activity and the ability of repeated IL-6 injections to produce long-lasting sensitization to the locomotor-stimulating effects of amphetamine suggest an interaction of this cytokine with the mesolimbic dopamine system, a system implicated in aspects of schizophrenia, addiction, and movement disorders. The fact that IL-6 caused a lasting change in responsiveness to amphetamine implies a mechanism by which immunogenic stimuli can alter brain circuitry, changing its sensitivity to seemingly unrelated subsequent stimuli or events.
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PMID:Interleukin-6 increases sensitivity to the locomotor-stimulating effects of amphetamine in rats. 1057 98

Several factors have been suggested in the etiopathology of schizophrenia, including autoimmune factors. Subgroup of schizophrenics have been found to have immunologic abnormalities. Evidence is presented of the role of lymphocytes and cytokine production in psychiatric disorders. Hypersecretion of IL-2 and IL-6 in acute exacerbation or in relapse-prone patients, decreased ratio of CD4+/CD8+, detection of antinuclear, anticytoplasmatic, antiphospholipid antibodies and others in chronic schizophrenic patients and lately the presence of antiphospholipid antibodies in unmedicated psychotic patients are examples of the immunologic abnormalities findings. These results suggest that schizophrenia may result from an immunologic disorder, which is mediated mainly (but probably not only) by lymphocyte dysfunction.
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PMID:Lymphocytes, autoantibodies and psychosis--coincidence versus etiological factor: an update. 1085 69

It has been postulated that altered interleukin (IL) regulation may be involved in the pathogenesis of schizophrenia. We therefore investigated the relationships between interleukins, neurotransmitters, and psychopathology in schizophrenia. IL-1beta, IL-2, IL-6, homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were measured in the plasma of neuroleptic-free male schizophrenics in comparison to age-matched healthy male controls (n=25 each). The patients' psychopathology was assessed by the Scale for the Assessment of Positive and Negative Symptoms (SAPS, SANS). The above variables were measured during acute states of illness and after eight weeks of treatment with haloperidol. The plasma levels of IL-2 and HVA were significantly higher in patients compared to controls. In schizophrenic patients, there were significant correlations between IL-2 and HVA, IL-2 and SAPS, and HVA and SAPS during the acute state of illness. The level of IL-6 was significantly correlated to SANS and duration of illness. In schizophrenic patients, the plasma levels of IL-2 and HVA were significantly lowered after treatment with haloperidol. Changes in IL-2 and HVA significantly correlated to those in HVA and SAPS, respectively. These results strongly suggest that the cytokines may modulate dopaminergic metabolism and schizophrenic symptomatology in schizophrenia.
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PMID:Relationships between interleukins, neurotransmitters and psychopathology in drug-free male schizophrenics. 1096 18

Prenatal exposure to infection appears to increase the risk of schizophrenia and other neurodevelopmental disorders. We have hypothesized that cytokines, generated in response to maternal infection, play a key mechanistic role in this association. E16 timed pregnancy rats were injected i.p. with Escherichia coli lipopolysaccharide (LPS) to model prenatal exposure to infection. Placenta, amniotic fluid and fetal brains were collected 2 and 8h after LPS exposure. There was a significant treatment effect of low-dose (0.5mg/kg) LPS on placenta cytokine levels, with significant increases of interleukin (IL)-1beta (P<0.0001), IL-6 (P<0.0001), and tumor necrosis factor-alpha (TNF-alpha) (P=0.0001) over the 2 and 8h time course. In amniotic fluid, there was a significant effect of treatment on IL-6 levels (P=0.0006). Two hours after maternal administration of high-dose (2.5mg/kg) LPS, there were significant elevations of placenta IL-6 (P<0.0001), TNF-alpha (P<0.0001), a significant increase of TNF-alpha in amniotic fluid (P=0.008), and a small but significant decrease in TNF-alpha (P=0.035) in fetal brain. Maternal exposure to infection alters pro-inflammatory cytokine levels in the fetal environment, which may have a significant impact on the developing brain.
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PMID:Prenatal exposure to maternal infection alters cytokine expression in the placenta, amniotic fluid, and fetal brain. 1116 42

Activation of the inflammatory response system and varied levels of cytokines in acute schizophrenia have been suggested by recent studies. Psychopharmacologic agents can differentially effect cytokine production, which suggests that therapeutic function of neuroleptics may involve immunomodulation. The present study was carried out to examine: (i) serum concentrations of interleukin (IL)-1beta, soluble interleukin-2 receptor (sIL-2R), IL-6, IL-8 and tumour necrosis factor (TNF)-alpha in schizophrenic patients; (ii) their relation with psychopathological assessment; and (iii) the relation of the initial cytokine levels with responsiveness to risperidone therapy. Thirty-four drug-free schizophrenic patients with acute exacerbation and 23 age- and gender-matched healthy controls were recruited for this study. Psychopathological assessments at admission and throughout risperidone treatment for 60 days were recorded. Serum cytokine concentrations were determined with chemilumunescence assays. According to our results, serum IL-1beta, sIL-2R, IL-6, IL-8 and TNF-alpha concentrations adjusted for age, gender, body mass index and smoking were no different in patients with schizophrenia and controls and among subtypes of schizophrenia. However, the initial TNF-alpha concentrations had a significant effect on Brief Psychiatric Rating Scale and Scale Assessment of Positive Symptoms scores. The initial cytokine concentrations of the patients responsive to risperidone were not significantly different from those of non-responsive patients. The present study demonstrates that plasma levels of IL-1beta, sIL-2R, IL-6, IL-8 and TNF-alpha adjusted for confounding factors are not altered in drug-free schizophrenic patients at acute exacerbation. We suggest that, if cytokine production is altered in schizophrenia, these alterations may not be detectable in systemic circulation. According to our results, the therapeutic effect of risperidone is not related to basal levels of the aforementioned cytokines. However, serum TNF-alpha may contribute to symptomatology in schizophrenia
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PMID:Serum IL-1beta, sIL-2R, IL-6, IL-8 and TNF-alpha in schizophrenic patients, relation with symptomatology and responsiveness to risperidone treatment. 1154 47

A variety of cytokines are dysregulated in schizophrenia, and some antipsychotic drugs effect cytokines. In order to examine the effect of risperidone on plasma cytokines, we measured the serum level of IL-1b, IL-2, IL-6, IL-12, and INF-g during acute states of illness, and after 4 weeks of treatment with risperidone in 19 schizophrenic patients. The patients' psychopathology was assessed by PANSS. Plasma IL-12 levels increased significantly after 4 weeks of treatment (p = .002). Plasma IL-b, IL-2, IL-6, and INF-g levels were not significantly different before and after treatment. There were no significant correlations between the changes in cytokine levels and the changes in PANSS scores. Increased IL-12 may contribute to activation of immune responses during treatment with risperidone. IL-12 may play an important role in immune responses related to neuropsychiatry.
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PMID:Effect of risperidone on serum cytokines. 1191 33

Cytokines have been one of the recent focal points of immunological research in schizophrenia. The present study was to assess the serum levels of some of interleukins in schizophrenia and their relationships with the psychopathological parameters. Seventy physically healthy Chinese patients, who met DSM-III-R criteria for schizophrenia and who were drug-free for at least 2 weeks, were compared with 30 age- and sex-matched Chinese normal controls. The psychopathology of schizophrenia was assessed by the Positive and Negative Syndrome Scale (PANSS). Serum levels of IL-6 and IL-8 were measured by sandwich enzyme-linked immunosorbent assay (ELISA), and serum IL-2 level was assayed by radioimmunometric assay (RIA). Serum levels of IL-2, IL-6 and IL-8 were significantly elevated in patients with a chronic form of schizophrenia (all p<0.05). There was a significant inverse relationship between IL-2 level and the PANSS positive subscale P (r=-0.31, p=0.006) and a significant positive correlation between IL-8 level and PANSS negative subscale N (r=0.25, p=0.036) in schizophrenic patients. In control subjects, a significant and positive relationship between serum IL-2 and IL-6 (r=0.513, p=0.004) was noted, whereas, there was a significant and negative relationship between IL-2 and IL-8 in schizophrenic patients (r=-0.28, p=0.02). Our data confirms and supports the view that immune disturbance is involved in schizophrenia, which is compatible with the possibility that Chinese schizophrenic patients have an ongoing autoimmune process. This immune disturbance is related to the subgroup of schizophrenic patients with characteristic clinical variables. The dysfunction of interaction or inter-adjustment between different cytokines may exist in schizophrenic patients.
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PMID:Elevated interleukin-2, interleukin-6 and interleukin-8 serum levels in neuroleptic-free schizophrenia: association with psychopathology. 1222 56

Infective agents (e.g., viruses) together with functional alterations of the immune system have been hypothesized to be implicated in the multifactorial pathogenesis of schizophrenia. The viral hypothesis of schizophrenia has been supported by the observation of birth peaks in winter seasons, prenatal exposure to virus epidemics and specific geographic patterns. On the other hand, not all the data published have shown consistent results supporting the immune hypothesis. Thus, it is likely that immune response factors may play a role in the pathogenesis of the disease only in specific subgroups of patients. The aim of the study was to investigate for the presence of differences of IL-6, IL-6R, gp130 and CC16 among four groups of chronic schizophrenic patients categorized according to the season of birth. We hypothesized that patients born in winter and spring would have had increased values of these cytokines. No significant differences were found among the four groups in any of the measures considered. These preliminary results appear to exclude a major role of the season of birth in determining reported interleukins system alterations in chronic schizophrenia.
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PMID:Season of birth and inflammatory response system in schizophrenia. 1292 23

It has been established that cytokines play a critical role in the regulation of the CNS and recent studies have suggested that dysfunctions of both pro-inflammatory (IL-1beta, IL-6, and TNF-alpha) and anti-inflammatory (IL-1RA and IL-10) cytokines could be involved in the pathophysiology of schizophrenia. Previous studies have reported that functional polymorphisms in some cytokines genes may have important regulatory effects on such system. Therefore, the aim of the present study was to explore the possible role of the IL-1beta -511C/T and IL-1RA (86bp)(n) repeats polymorphisms in schizophrenia. A case control association study comparing genotype and allele frequencies in 346 northen Italian subjects (169 schizophrenic patients and 177 unrelated healthy volunteers) was performed. The frequencies of IL-1beta -511C and IL-1RA allele 1 (86bp)(4) are significantly higher in schizophrenic patients compared to controls (IL-1beta -511 P=0.047; IL-1RA (86bp)(n) P=0.002). Moreover our data show a protective effect of the IL-1RA allele 2 (86bp)(2) against schizophrenia (OR=0.59 95%CI:0.388-0.910; P=0.016) and this effect is enhanced by the concomitant presence of IL-1beta -511T (OR=0.48 95%CI:0.30-0.76; P=0.002). Our findings support the hypothesis that genetically determined changes in IL-1 metabolism regulation may contribute to the pathogenesis of schizophrenia confirming a role of IL-1 gene cluster in disease susceptibility.
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PMID:Association between IL-1beta -511C/T and IL-1RA (86bp)n repeats polymorphisms and schizophrenia. 1456 76

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


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