Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Elevated circulating levels of IL-6 in schizophrenia. 882 53

There is a strong interrelationship between the immune system, the central nervous system and psychological processes that are suggested to play a pivotal role in the pathogenesis of psychiatric disorders. In schizophrenia and depression, activation of the immune system has been observed repeatedly. Cytokines play a key role in immune activation. They are actively transported into the CNS, but also released from activated glia cells. Cytokines activate glia cells in the CNS to produce other cytokines, and a cascade of cytokine effects may be initiated by this mechanisms. During the past few years, the influence of the cytokines on dopaminergic, noradrenergic and serotonergic neurotransmission and also on the hormones of the hypothalamus-pituitary-adrenal axis has been elucidated. It suggests a pivotal role in psychological processes and psychiatric disorders. For example, in schizophrenia the IL-2 cerebrospinal fluid concentration shows a stronger relationship to the relapse probability than catecholamine metabolites. Although the hypersecretion of IL-2 in schizophrenia and of IL-6 in depression are suggested to play key roles for these disorders, a specificity of certain cytokines for certain psychiatric disorders seems unlikely. Psychomotor, sleep and sickness behavior are influenced by IL-1, disturbances of memory and attention by IL-2, but also by TNF-alpha. From the distribution of cytokine receptors in the CNS conclusions can be drawn regarding the influence of cytokines on psychological processes. The finding that norepinephrine stimulates activated astrocytes to produce IL-6 implies that the cytokine cascade may be activated by neuronal processes under certain conditions. This can lead to a molecular biological explanation of the influences of stress on the immune system. Lastly, influences of the cytokines on blood-brain barrier disturbances and further consequences resulting from the role of the cytokine network in the CNS are discussed.
 ...
PMID:[Role of the cytokine network in the CNS and psychiatric disorders]. 913 17

This study examines cerebrospinal fluid from patients with three neuropsychiatric diseases of childhood for the presence and levels of several cytokines relevant to cell-mediated (type 1) and humoral (type 2) immunity. The patient groups include childhood-onset schizophrenia (n = 22), obsessive-compulsive disorder (OCD) (n = 24), and attention deficit hyperactivity disorder (n = 42). The cytokines examined include IL-2, IFN-gamma, TNF-beta/LT, IL-4, IL-5, IL-10, and TNF-alpha. Patients with OCD had a preponderance of type 1 cytokines. IL-4 was detectable only in samples from patients with schizophrenia. IL-10 was rarely detected and never in patients with OCD. Few patients with schizophrenia had detectable amounts of IFN-gamma in CSFL. We conclude that there is a relative skewing of CSFL profiles toward type 1 cytokines in patients with OCD, whereas in schizophrenia the relative preponderance is toward type 2 mediators. Patients with attention deficit hyperactivity disorder exhibited profiles intermediate between OCD and schizophrenia. We infer that cell-mediated immunity may be involved in the etiopathogenesis of OCD, whereas a relative lack of cell-mediated immunity and involvement of humoral immunity may be present in schizophrenia. These data provide a rationale for immune-based strategies of study and therapeutics in childhood neuropsychiatric disease.
 ...
PMID:Cerebrospinal fluid cytokines in pediatric neuropsychiatric disease. 930 Jul 24

1. Parallel to the current rapid development of new immunological methods, immune mechanisms are gaining more importance for our understanding of psychiatric disorders. The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system. 2. The topical literature dealing with the interactions of immune system, neurotransmitters, psychological processes, and psychiatric disorders, especially in relation to cytokines, is reviewed. 3. An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described. Cytokines, actively transported into the CNS, play a key role in this immune activation. It was recently observed that cytokines activate astrocytes and microglia cells, which in turn produce cytokines by a feedback mechanism. Moreover, they strongly influence the dopaminergic, noradrenergic, and serotonergic neurotransmission. 4. There are indications that the cascade of cytokines can be activated by neuronal processes. These findings close a theoretical gap between stress and its influence on immunity. Psychomotor, sickness behavior and sleep are related to IL-1; disturbances of memory and cognitive impairment are to IL-2, in part also to TNF-alpha. The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia, and IL-6, on depressive disorders. 5. Although single cytokines most likely do not have a specificity for certain psychiatric disorders, a characteristic pattern of cytokine actions in the CNS, including influences of the cytokines on the blood-brain barrier, seems to play a role in psychiatric disorders. This may have therapeutic implications for the future.
 ...
PMID:Psychoneuroimmunology and the cytokine action in the CNS: implications for psychiatric disorders. 953 65

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
 ...
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

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.
 ...
PMID:Association between IL-1beta -511C/T and IL-1RA (86bp)n repeats polymorphisms and schizophrenia. 1456 76

Celecoxib augmentation therapy has been reported to enhance the rate of clinical response for patients with schizophrenia. This may be due in part to an effect of celecoxib in the immune dysfunction associated with schizophrenia. Given concerns about the safety of COX-2 inhibitors, studies investigating cytokine levels in medicated patients with schizophrenia are of public health importance. Twenty-eight schizophrenia subjects stabilized on olanzapine or risperidone were randomized to receive 8 wk of celecoxib (400 mg/d) or placebo. Serum soluble IL-2 receptor (sIL-2r) and in-vitro PHA-stimulated whole-blood cytokine production levels were measured at baseline, 1 wk, and 8 wk. Celecoxib augmentation did not alter any of the cytokine parameters measured for the overall study group. However, 1 wk of celecoxib augmentation increased TNF-alpha and IL-2 production levels in olanzapine-treated subjects. These elevations did not persist by week 8. Overall, celecoxib does not significantly modify cytokine levels in medicated schizophrenia subjects.
 ...
PMID:The effects of celecoxib augmentation on cytokine levels in schizophrenia. 1603 56

Schizophrenia is perhaps the most enigmatic and tragic psychotic disorder with remarkable mortality and morbidity. Schizophrenia is complex and clinically a heterogeneous disorder. The etiological basis of schizophrenia ranges from autoimmune to neurodevelopmental hypothesis in one hand and involvement of different major gene segment with susceptibility loci on the other. Recently, neurodevelopmental hypothesis gained much impetus over the other domain. To support the neurodevelopmental basis, a number of investigations have shown that maternal infections during pregnancy increases the risk of the offspring developing schizophrenia and other neurodevelopmental disorders. The pathological mechanisms underlying this phenomenon is largely unknown. Many have suggested the involvement of different immune markers and shown that cytokines generated in response to maternal infection alter early brain development through their inflammatory activity. However, these findings have escaped discussion on various important issues related to cytokine homeostasis which depends on a large number of immune parameters including non-classical HLA-G molecules. Infections during early stages of pregnancy may alter cytokine regulation by disturbing the whole uterine immune milieu. To elucidate this issue, authors have tried to correlate the possible relationships between maternal infections and aberration of immune networking at the feto-maternal interface and their subsequent influence on the structural and functional abnormalities of the developing brain. The authors hypothesize that there exists a counter regulatory interaction among proinflammatory cytokines like TNF-alpha, HLA-G molecules and different immune cells like NK cells. We emphasize that HLA-G molecules are the novel immune players which maintain the immune homeostasis during early pregnancy in a manner that it can protect developing fetus from maternal immune attack. However, maternal infections may lead to the disturbance of HLA-G expression which in turn may fail to maintain its otherwise inhibitory potential to down regulate the detrimental inflammatory cytokines. Investigation on such interaction may unravel novel molecular mechanisms of neurodevelopmental basis of schizophrenia. Testing of our proposed hypothesis on animal models and on in vitro derived extravillous trophoblast cell lines holds promise of great insights to usher a new dimension of schizophrenia research and for developing new therapeutic strategies for better treatment and to adopt genetic prediction in schizophrenia management paradigm.
 ...
PMID:The role of HLA-G in cytokine homeostasis during early pregnancy complicated with maternal infections: a novel etiopathological approach to the neurodevelopmental understanding of schizophrenia. 1618 9

Maternal infections with bacterial or viral agents during pregnancy are associated with an increased incidence of schizophrenia in the offspring at adulthood although little is known about the mechanism by which maternal infection might affect fetal neurodevelopment. Exposure of pregnant rodents to the bacterial endotoxin, lipopolysaccharide (LPS), results in behavioral deficits in the adult offspring that are relevant to schizophrenia. It is however unknown whether these effects are due to the direct action of the inflammatory stimulus on the developing fetus, or due to secondary immune mediators (cytokines) activated at maternal/fetal sites. In this study we sought to elucidate the site of action of LPS, following a single intraperitoneal (i.p.) injection, in pregnant rats at gestation day 18. Animals received 5 muCi of iodinated LPS ((125)I-LPS) and its distribution was assessed in maternal/fetal tissues (1-8 h). In addition, induction of the inflammatory cytokines, TNF-alpha, IL-1beta and IL-6, was measured in maternal/fetal tissues following maternal LPS challenge (0.05 mg/kg, i.p.) (2-8 h). (125)I-LPS was detected in maternal tissues and placenta, but not the fetus. This distribution was accompanied by significant increases in TNF-alpha, IL-1beta and IL-6 in maternal plasma and placenta, but not in fetal liver or brain. A significant increase in IL-1beta was however detected in fetal plasma, possibly due to transfer from the maternal circulation or placenta. Collectively, these data suggest that effects of maternal LPS exposure on the developing fetal brain are not mediated by the direct action of LPS, but via indirect actions at the level of the maternal circulation or placenta.
 ...
PMID:The role of cytokines in mediating effects of prenatal infection on the fetus: implications for schizophrenia. 1618 9

Immune hypothesis of schizophrenia fits well with the supposed interaction between genetic and environmental factors in understanding its complicated pathogenesis that is not be able to be explained by any one supposed hypothesis. Prenatal infections have been also suggested to be associated with schizophrenia in which cytokines may play a critical role in the translation of prenatal infection to develop schizophrenia. Moreover, antipsychotics are known to have direct or indirect effects on the immune system. Among cytokines, the immunomodulatory functions of lymphotoxin-alpha (tumor necrosis factor (TNF)-beta) is well known and could come up with the pathophysiology of schizophrenia. It affects and modulates production of other cytokines such as TNF-alpha and IL-6 which are consistently proposed to be involved in the development of schizophrenia. TNF-beta is also crucial to prevent prenatal infections. In addition, TNF-beta is effective in the protection of neuronal cells against glutamate and NMDA toxicity which is considered a neurodevelopmental hypothesis of schizophrenia. Moreover, it was also found to be associated with the regulation of glial cells and stimulation of the synthesis and secretion of nerve growth factors (NGFs) in the CNS. Finally, TNF-beta gene is located on the short arm of chromosome 6 (6p21.1-6p21.3), where is a possible susceptibility locus for schizophrenia. Therefore, TNF-beta may provide a new insight for understanding schizophrenia, providing a more systematic organization of immunological contributing factors to the development of schizophrenia.
 ...
PMID:Potential role of lymphotoxin-alpha (tumor necrosis factor-beta) in the development of schizophrenia. 1714 Jul 46


1 2 3 Next >>