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)

Chronic macrophage activation with subsequent failure of activated macrophages to properly control T-lymphocyte secretion of interleukin-2 and interleukin-2 receptors is proposed as the basic biological mechanism of schizophrenia. Fundamental to this theory are the clinical observations on interleukin-2 provoking the active phase symptoms of schizophrenia in psychiatrically normal human volunteers and macrophage cytokines producing the prodromal and residual phase symptoms. This theory provides a completely new and unified mechanisms for the antipsychotic action of typical and atypical neuroleptics, bromocriptine, naloxone and DMSO. Furthermore, this hypothesis reveals why the dopamine theory of schizophrenia was a false lead. The effects of prolactin, estrogens and androgens are consistent with the model. Age of onset, male/female incidence, course of the disease from prodromal to active to residual phase, the protection afforded by rheumatoid arthritis and the close relationship between depression and schizophrenia can be explained by this theory. The gastrointestinal tract is suggested as the preferred site to investigate for the cause of the immune activation in schizophrenia.
 ...
PMID:A comprehensive macrophage-T-lymphocyte theory of schizophrenia. 136 59

In schizophrenia, various modifications of the immune system have been reported. A decrease of interleukin-2 production by T lymphocytes and an increase of IL-2 receptors were observed by several authors. Not only cellular but humoral immunity seems to be modified: apart from the viral hypothesis, an auto-immune hypothesis holds that auto-antibodies may play a role in the biology of schizophrenia. Natural auto-antibodies, preexisting any antigenic stimulation, may also be involved, particularly in the response to neuroleptic drugs.
 ...
PMID:[Schizophrenia and immunity]. 136 90

Mitogen-stimulated interleukin-2 (IL-2) production was measured in 122 patients who met Research Diagnostic Criteria for schizophrenia and 98 normal control subjects. The presence of autoantibodies against seven common antigens was also determined. There was no relationship between the presence of circulating autoantibodies and IL-2 production in control subjects. In patients, however, autoantibody-positive, acutely ill patients had significantly lower IL-2 production as compared with other patients and control subjects. Never-medicated patients showed the same trends for decreased IL-2 production in association with autoantibodies. These data suggest that decreased IL-2 production is associated with acute illness in schizophrenic patients who produce autoantibodies, a trait known to be associated with increased vulnerability to autoimmune disease.
 ...
PMID:Altered interleukin-2 production in schizophrenia: association between clinical state and autoantibody production. 148 Jun 77

Schizophrenic patients have low concentrations of PGE-1, n-6 fatty acids, vitamin C and zinc, elevated brain levels of dopamine and high plasma levels of interleukin-2 receptors (IL-2R). IL-2R plasma titers can be raised in celiac patients by administering wheat. These findings are both consistent with and supportive of the GI T-lymphocyte theory of schizophrenia.
 ...
PMID:The GI T-lymphocyte theory of schizophrenia: some new observations. 156 3

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

The immune system is proposed as the key to understanding the etiology and treatment of psychosocial disease. There is a dense communication network between the immune system and the central nervous system (CNS). Immune cell cytokines, via direct action on the CNS, induce fever, alter sleep, pain perception and pituitary hormone release and reduce appetite and activity in animals. Interleukin-2 and interferon given to humans result in global behavioral and cognitive pathology. Activation of the immune system by pathogens produces global cognitive and behavioral pathology also. Recently, controlled trials have demonstrated that diet can cause psychosocial disease, presumably by an immune mechanism. Immune system abnormalities have been identified in manic-depressive psychosis, schizophrenia and alcoholism. Lithium carbonate is not only prophylactic for all three of these diseases, but it also powerfully stimulates the immune system. This is proposed as the mechanism of lithium's therapeutic effect. The antipsychotics, haloperidol and the phenothiazines, affect the immune system also. The rapid development of AIDS dementia complex can be explained by the remarkable influence the immune system has on the CNS.
 ...
PMID:The immune system is a key factor in the etiology of psychosocial disease. 205 27

Excessive production of interleukin-2 (IL-2) and IL-2 receptors (IL-2R) by gastrointestinal (GI) T-lymphocytes is hypothesized as the cause of schizophrenia. It is based on: 1) IL-2 given to human volunteers can cause all the symptoms of schizophrenia; 2) GI lymphocytes in nonhuman primates produce much more IL-2 and IL-2R when stimulated than peripheral blood lymphocytes; 3) the GI tract is the largest lymphoid 'organ' in the body. The hypothesis appears to: 1) explain the protective effect of rheumatoid arthritis on schizophrenia; 2) make mechanistically plausible the findings on wheat and schizophrenia; 3) be consistent with and explain many of the known immunological abnormalities in schizophrenia.
 ...
PMID:Is schizophrenia caused by excessive production of interleukin-2 and interleukin-2 receptors by gastrointestinal lymphocytes? 206 56

Recently, several lines of evidence have suggested the possible of immunological dysfunction in the pathogenesis of schizophrenia. We therefore investigated the ability to produce interferons and lymphokines in response to mitogenic or viral stimulation in a whole blood assay of 37 schizophrenic patients (DSM-III-R) and of 42 healthy blood donors. Phytohaemagglutinin (PHA) was used for the induction of interleukin-2 (IL-2), interferon gamma (INF gamma), interleukin-6 (IL-6) and the soluble interleukin-2 receptor (sIL-2R) and Newcastle Disease Virus (NDV) for the induction of interferon alpha 2 (INF alpha 2). All lymphokines and, in addition, the sIL-2R in the sera were determined by ELISA technique. The psychopathological status of the patients was assessed by psychiatrists according to internationally accepted standards. The patient group showed a trend to lower levels of the interferons alpha 2 and gamma and a significant decrease of IL-2 production. The sIL-2R levels were significantly increased in the sera of schizophrenic patients. The latter increase was associated with a poor assessment of prognosis (Strauss and Carpenter). This association appears to be of interest. However, its significance is not understood, since longitudinal studies could not be performed.
 ...
PMID:Production of interferons and lymphokines in leukocyte cultures of patients with schizophrenia. 754 76

Levels of CSF fluid interleukin-2, but not interleukin-1 alpha, were found to be higher in 10 neuroleptic-free schizophrenic patients than in 10 healthy subjects matched for sex and age. Because interleukin-2 increases dopaminergic neurotransmission and participates in autoimmunity and cell growth, the authors postulate that elevated levels of central interleukin-2 might contribute to the increased dopaminergic neurotransmission, autoimmune phenomena, and abnormal brain morphology described in some patients with schizophrenia.
 ...
PMID:Elevated CSF levels of interleukin-2 in neuroleptic-free schizophrenic patients. 810 12

The pathophysiology of psychotic and other symptoms in schizophrenia remains a mystery despite decades of research. Even though it has been suspected for many years that autoimmune mechanisms may play a role in the pathophysiology of schizophrenia, firm evidence for this hypothesis has been lacking. Our studies, over the last 10 years, have revealed that a subgroup of schizophrenics have several significant immunological abnormalities, including increased prevalence of autoimmune diseases and of antinuclear antibodies (ANA) and anticytoplasmic antibodies (ACA), decreased lymphocyte interleukin-2 (IL-2) production, increased serum IL-2 receptor concentration, increased serum IL-6 concentration, and an association with HLA antigens. These findings are characteristic of autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis and insulin-dependent diabetes mellitus. We also found that some schizophrenics have antibodies to hippocampal antigens (AHA) in their serum, together with lowered IL-2 production. None of the above findings can be interpreted as definitely confirming the role of autoimmunity in schizophrenia. Nevertheless, taken together, the recent evidence points towards the existence of a subgroup of schizophrenics who have immunological findings consistent with that hypothesis. Further studies directed at finding the brain antigens targeted by the immune system in these patients, and longitudinal studies correlating clinical and immune changes over time, are needed.
 ...
PMID:Autoimmunity in schizophrenia: a review of recent findings. 825 Nov 50


1 2 3 4 5 Next >>