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)

The hypothesis of an immunological defect in schizophrenia has been supported by reports on abnormal production of interleukin-2 (IL-2) and interferons (IFNs) in schizophrenic patients. In the present study we determined the serum concentrations of IL-2, IFN-alpha and IFN-gamma in 10 first onset, neuroleptic-naive schizophrenics, in 6 pretreated patients who were drug free (1 week to 2 years) at the time of the investigation and in 15 matched healthy controls. No IFN-alpha was detected in schizophrenics' and in control sera. No differences were found in IL-2 and IFN-gamma levels between schizophrenics and controls. Thus the present study failed to support the hypothesis of an immunological abnormality in schizophrenia on the basis of the determination of IL-2 and IFNs serum levels.
 ...
PMID:Abnormalities in serum concentrations of interleukin-2, interferon-alpha and interferon-gamma in schizophrenia not detected. 157 15

Production of interferon (IFN)-alpha and -gamma by leukocytes from 34 patients with acute schizophrenia and 34 controls was measured before and after 5-6 weeks of antipsychotic treatment by using Sendai virus as IFN-alpha inducer and lentil lectin as inducer for IFN-gamma production. The schizophrenia series included 13 first admission patients (mean duration of illness 1.1 years) and 21 re-entry patients (mean duration of illness 10.1 years). Of the total series 23 were drug-free at the time of pretreatment sampling. In all subgroups the schizophrenic patients produced less IFNs than healthy controls although the differences reached statistical significance only in the total group of schizophrenic patients with regard to production of IFN-alpha. The antipsychotic drug treatment did not have an effect on IFN production. The techniques used, the influence of genetic factors, and eventual clinical implications are discussed.
 ...
PMID:Production of interferon-alpha and gamma by leukocytes from patients with schizophrenia. 251 35

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

Recent findings have strengthened the hypothesis that immunological dysfunctions may contribute towards the multifactorial pathogenesis of schizophrenia. The validity of these findings is questioned by the fact that most studied subjects have received potentially immunomodulatory medication upon investigation. In order to rule out such confounding effects, 24 initially unmedicated acutely ill schizophrenic patients were studied immunologically and psychiatrically (PANSS) before and during 4 weeks of neuroleptic treatment. The production of IFN-gamma was decreased upon admission and after 2 weeks of treatment compared to matched healthy controls. No differences in IL-2 and IFN-gamma production between unmedicated and medicated states were observed. These results do not support the notion that neuroleptic medication in vivo might influence TH1 cytokine production in schizophrenia.
 ...
PMID:Cytokine production in unmedicated and treated schizophrenic patients. 1105 7

Alterations of cytokine levels represent the most consistent finding from studies concerning the involvement of the immune system in the etiology of schizophrenia. These results have been discussed controversially due to the potential influence of drug treatment on cytokine production and on the experimental procedures used for cytokine measurement. In the present study, the influences of typical and atypical neuroleptic drugs (haloperidol and clozapine) as well as a tricyclic antidepressive drug (amitriptyline) on cytokine levels (IL-2 and IFN-gamma) were examined in vitro in a whole blood assay under various conditions of phytohemagglutinin (PHA) stimulation and drug incubation. Stimulation was enhanced by haloperidol and clozapine, but not by the antidepressant, meaning that the results of decreased cytokine levels seen in earlier studies in schizophrenic patients cannot be explained through drug influences alone. Furthermore, our findings allow us to conclude that, in contrast to the antidepressant drug, the typical and atypical neuroleptic drugs seem to influence the examined cytokine levels.
 ...
PMID:The influence of typical and atypical neuroleptic drugs in the production of interleukin-2 and interferon-gamma in vitro. 1256 34

Microglia has recently been regarded to be a mediator of neuroinflammation via the release of proinflammatory cytokines, nitric oxide (NO) and reactive oxygen species (ROS) in the central nervous system (CNS). Microglia has thus been reported to play an important role in the pathology of neurodegenerative disease, such as Alzheimer's disease (AD) and Parkinson's disease (PD). The pathological mechanisms of schizophrenia remain unclear while some recent neuroimaging studies suggest even schizophrenia may be a kind of neurodegenerative disease. Risperidone has been reported to decrease the reduction of MRI volume during the clinical course of schizophrenia. Many recent studies have demonstrated that immunological mechanisms via such as interferon (IFN)-gamma and cytokines might be relevant to the pathophysiology of schizophrenia. In the present study, we thus investigated the effects of risperidone on the generation of nitric oxide, inducible NO synthase (iNOS) expression and inflammatory cytokines: interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha by IFN-gamma-activated microglia by using Griess assay, Western blotting and ELISA, respectively. In comparison with haloperidol, risperidone significantly inhibited the production of NO and proinflammatory cytokines by activated microglia. The iNOS levels of risperidone-treated cells were much lower than those of the haloperidol-treated cells. Antipsychotics, especially risperidone may have an anti-inflammatory effect via the inhibition of microglial activation, which is not only directly toxic to neurons but also has an inhibitory effect on neurogenesis and oligodendrogenesis, both of which have been reported to play a crucial role in the pathology of schizophrenia.
 ...
PMID:Risperidone significantly inhibits interferon-gamma-induced microglial activation in vitro. 1736 22

A growing body of evidence suggests that changes in the serum levels and cellular production of various cytokines are associated with the immunological abnormalities of schizophrenia. Several studies have examined alterations in T helper type 1 (Th1) and T helper type 2 (Th2) cytokines in schizophrenia. We explored monocytic, Th1 and Th2 cytokines in 43 schizophrenia patients and 50 normal controls. The mitogen-induced production of tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), IL-4, gamma-interferon (IFN-gamma) and IL-2 was measured with enzyme-linked immunosorbent assays before and after antipsychotic treatment. IL-6 and TNF-alpha production by schizophrenic patients was significantly higher than by normal controls, while IL-2, IL-4 and IFN-gamma production was significantly lower in schizophrenic patients. After 6 weeks of antipsychotic treatment, IL-6 and TNF-alpha production was significantly decreased, while IL-4, IFN-gamma and IL-2 productions were not significantly changed. Our results suggest that increased monocytic cytokines and decreased Th1 and Th2 cytokines may be associated with the immunopathogenesis of acute psychotic schizophrenia, and that antipsychotics may play an important role in immune response by decreasing elevated monocytic cytokines.
 ...
PMID:Monocytic, Th1 and th2 cytokine alterations in the pathophysiology of schizophrenia. 1803 15

The activation of the inflammatory/immunological response system is suggested to be related to the pathophysiology of schizophrenia. Aripiprazole is a novel atypical antipsychotic, which is a high-affinity dopamine D(2) receptor partial agonist. Atypical antipsychotics, all of which have dopamine D(2) receptor antagonism, have recently reported to have significantly inhibitory effects on interferon (IFN)-gamma-induced microglial activation in vitro. In the present study, we investigated whether or not aripiprazole also has anti-inflammatory effect on IFN-gamma-induced microglial activation. Not quinpirole, dopamine D(2) full agonist, but aripiprazole significantly inhibited the generation of nitric oxide (NO) and tumor necrosis factor (TNF)-alpha from IFN-gamma-activated microglia and suppressed the IFN-gamma-induced elevation of intracellular Ca(2+) concentrations ([Ca(2+)](i)) in murine microglial cells. Increased [Ca(2+)](i) has been reported to be required, but by itself not sufficient, for the release of NO and certain cytokines. As a result, we can speculate that aripiprazole may inhibit IFN-gamma-induced microglial activation through the suppression of IFN-gamma-induced elevation of [Ca(2+)](i) in microglia. Our results demonstrated that not only antipsychotics which have dopamine D(2) receptor antagonism but also aripiprazole have anti-inflammatory effects via the inhibition of microglial activation. Antipsychotics may therefore have a potentially useful therapeutic effect on patients with schizophrenia by reducing the microglial inflammatory reactions.
 ...
PMID:Inhibitory effects of aripiprazole on interferon-gamma-induced microglial activation via intracellular Ca2+ regulation in vitro. 1842 30

Nervous and immune system interact through many different messenger substances such as neurotransmitters, cytokines or neuropeptides. For instance, neuropeptides are capable of affecting the metabolism of cells belonging to the immune system. Conversely, cytokines such as tumor necrosis factor (TNF)-alpha, interferon (IFN)-alpha and IFN-gamma, contribute to the receptor resistance of neuropeptides, reduce the availability of amino acids which are needed for the synthesis of neurotransmitters or show neurotoxic effects. Other cytokines like granulocyte-colony stimulating factor (G-CSF) may be highly attractive candidates for the treatment of neurodegenerative conditions. Cytokines are decisively involved in the pathophysiology of psychiatric disorders such as depression, schizophrenia or anorexia nervosa as well as in neurological, respectively neurodegenerative diseases like Parkinson's or Alzheimer's. This connection between the immune system and the pathogenesis of psychiatric disorders leads to the concept that immunomodulatory drugs which are already in use for various diseases related to the immune system may also be efficient in the treatment of psychiatric disorders. This article is supposed to give an overview over the current concepts and possibilities since hopefully these hypotheses lead to new therapeutical strategies for psychiatric patients in the future.
 ...
PMID:Anti-inflammatory drugs in psychiatry. 1975 10