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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Based on a review of the literature, the article deals with the major biological markers of schizophrenia. Recent developments in molecular biology have shown a possible association between schizophrenia and various HLA markers (A1, A2, A9, A10, A28, B27, BW16), and a linkage--in several families--between the disease and some polymorphisms of chromosome 5. On the other hand, chromosome X might also be involved. Neuropathological abnormalities have often been found in the brains of schizophrenics, such as cellular alterations in the basal ganglia and the limbic structures. Investigations by means of CT-scan and Magnetic Resonance Imaging have pointed out an enlargement of cerebral ventricles and/or an atrophy of frontal areas, especially amongst patients with prominent negative symptoms. The dopaminergic hypothesis of schizophrenia reposes on the major following facts: the therapeutic efficiency of neuroleptics (dopaminergic antagonists); a positive correlation between plasma homovanillic acid (metabolite of dopamine) concentration and the severity of schizophrenic illness; a higher density of dopaminergic D2-receptors (revealed by Positron Emission Tomography thanks to specific radioligands), particularly in the striatum; and an abnormal plasmatic growth-hormone response to apomorphine (dopaminergic agonist). Central noradrenergic dysfunctions might also occur in paranoid schizophrenia, as underlined by higher cerebrospinal fluid levels of norepinephrine, and a lack of decrease of plasma 3-methoxy-4-hydroxy-phenylglycol (MHPG, metabolite of norepinephrine) after clonidine (alpha-2-adrenergic agonist) dispensation. Nevertheless, in patients with predominating negative symptoms, this is a trouble in serotoninergic functions which has been suggested. In the field of immunology, some findings such as alteration in lymphocytes populations (T4/T8, CD5), anti-cerebral auto-antibodies, abnormal lymphocytes responses to mitogens, decreased production of interleukin-2, have lead to two main hypotheses: autoimmunity and immunologic incompetence. On the other hand, electrophysiological studies have shown a hypovariability of alpha-rythm on the EEG; a lower amplitude of the component P300 from visual evoked potentials; sleep disorders such as a shorter rapid eye movement sleep latency and a decreased total slow-wave sleep percent; irregular smooth pursuit eyes-movements; an electrodermal response according to either the hyper-responder either the non-responder type. At last, troubles in sensory integration, motor coordination and attention have also been demonstrated. All those many findings outline the heterogeneity of schizophrenic disorders.
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PMID:[Biological markers in schizophrenia]. 830 20

There is a confusing history of immune findings associated with schizophrenia. At least some of these discrepant results may be artifacts caused by heterogeneity. In an attempt to decrease heterogeneity, we studied three groups of monozygotic twins who were either discordant for schizophrenia, concordant and ill, or concordant and well. This comparison minimizes environmental and genetic variance, and heightens differences that are actually due to the disorder. Overall, schizophrenic subjects had higher levels of serum soluble interleukin-2 receptors (SIL-2Rs) than unaffected individuals (480.8, SD 238.6 U/ml vs 380.9, SD 170.6 U/ml; F = 5.256, df = 1.61, P = 0.02). When data from discordant and concordant twin groups were analysed separately, both the discordant ill twins (P = 0.06) and concordant ill twin pairs (P = 0.08) showed trends towards higher serum SIL-2R levels than their respective control groups. These data contribute to the growing body of evidence that immune activation is associated with some forms of schizophrenia.
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PMID:Increased serum soluble interleukin-2 receptors in schizophrenic monozygotic twins. 839 12

1. It has been postulated that the interrelated processes of neurodegeneration, neuroplasticity, and neuroimmunological abnormalities may play a role in the pathophysiology of schizophrenia. Since, interleukins are produced in the central nervous system and have cytokine and growth promoting properties, they are an obvious choice to consider in these neural processes. 2. Cerebrospinal fluid obtained from schizophrenic patients, on and off medications, and from normal controls was assayed for interleukin-1 alpha (IL-1 alpha) and interleukin-2 (IL-2) using a sensitive enzyme-linked immunoassay. 3. IL-1 alpha concentration were below the detection limits of the assay in both controls and schizophrenics. 4. IL-2 levels were under 1 ng/ml CSF in nearly all subjects. There was no significant difference in IL-2 levels between medicated and medication-free schizophrenics or when patients were compared to controls.
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PMID:Interleukin-1 alpha and interleukin-2 in cerebrospinal fluid of schizophrenic subjects. 847 20

Chronically activated macrophages and T-lymphocytes, along with excessive interleukin-2 and other cytokine secretions, were previously proposed as the fundamental mediators of schizophrenia. This paper provides further support for the immune model of schizophrenia, including evidence on neurotransmitter abnormalities, the low amplitude of the auditory P300 event-related potential, the neurodevelopmental model of schizophrenia and the possible involvement of the locus ceruleus in schizophrenia.
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PMID:The macrophage-T-lymphocyte theory of schizophrenia: additional evidence. 853 36

In an attempt to define potential immunological dysfunctions in schizophrenia, we determined the production of interleukin-2 (IL-2), interleukin-4 (IL-4), interferon-gamma (IFN-gamma), and soluble IL-2 receptor (sIL-2R) in a whole-blood assay after stimulation with phytohemagglutinin (PHA) as well as the serum concentrations of sIL-2R. Because CD4+CD45RO+T cells are the main producers of IFN-gamma, we determined the percentage of these cells, as well as of panT, CD4+T, and CD8+T cells, by flow cytometry. A whole-blood count was performed in addition. Two groups of patients were examined, paranoid-type and residual-type schizophrenics. The numbers of both monocytes and neutrophils, but not of lymphocytes, were increased significantly in the schizophrenic sample. The IFN-gamma production of the schizophrenics as a whole group, and of the paranoid patients, was reduced significantly in comparison with the control group (p < or = 0.05). The residual patients produced less IFN-gamma than the controls, but more than the paranoid patients. The latter differences did not reach statistical significance. The production of IL-4, which physiologically antagonizes the production of IFN-gamma, was not significantly higher in the patient group. No changes in the lymphocyte subpopulations were observed. The production of IL-2 showed a trend toward reduction in paranoid patients, but not in residual schizophrenics. The serum sIL-2R levels were elevated slightly in schizophrenics when compared with controls. In order to rule out a possible effect of cortisol on cytokine production, 20 schizophrenics were compared with 20 age- and gender-matched controls. However, neither elevated cortisol levels were detected in the schizophrenic sample, nor significant intercorrelations between cortisol levels and cytokine production, or levels of sIL-2R, respectively. In summary, our data reinforce the possibility of immune dysfunction in schizophrenia and point to the possible relevance of disease subgroups in this respect.
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PMID:Investigations of cytokine production in whole blood cultures of paranoid and residual schizophrenic patients. 886 7

The paper is a review of the literature on cellular and humoral immunity in schizophrenic patients. The reports have revealed that there are manifestations of autoimmunological process in a subgroup of schizophrenics (among others: increased serum level of specific and non-specific autoantibodies, decreased lymphocyte interleukin-2 production, increased soluble IL-2 receptor concentration, increased serum IL-6 level, presence of lymphocyte abnormalities and association with HLA antigens. It is suggested that virus infection may provoke the appearance of autoimmunological reaction, while genetic factors might increase some predisposition to this reaction. The reports have also revealed that autoimmunity may play a role in pathogenesis of schizophrenia in a subgroup of schizophrenic patients who have immunological abnormalities.
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PMID:[Changes of humoral and cellular immunity in schizophrenia]. 898 18

This study investigated immune activation, as measured by production of interleukin-2 (IL-2) and soluble interleukin-2 receptors (sIL-2R) from stimulated lymphocytes, in schizophrenia and schizophreniform disorder. The study included 13 neuroleptic-free patients, 13 medicated patients and 13 age- and sex-matched control subjects. Production of IL-2 and sIL-2R by peripheral blood mononuclear cells (PBMCs) was measured after in vitro stimulation with phytohaemagglutinin (PHA). Patients' symptoms were rated on the Scales for Assessment of Positive (SAPS) and Negative Symptoms (SANS) and the Brief Psychiatric Rating Scale (BPRS). IL-2 production by stimulated lymphocytes was significantly elevated in neuroleptic-free patients compared with both medicated patients and control subjects. IL-2 production was inversely correlated with the SAPS subscales of bizarre behaviour and formal thought disorder. The pattern of increased IL-2 production is in contrast to previous findings in patients with schizophrenia. Significant associations with clinical rating scores suggest that IL-2 production may vary in different biological subgroups of schizophrenia and schizophreniform disorder.
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PMID:Increased production of interleukin-2 (IL-2) but not soluble interleukin-2 receptors (sIL-2R) in unmedicated patients with schizophrenia and schizophreniform disorder. 1071 Jan 77

Interleukin-2 (IL-2) has recently been implicated as a modulator of brain neuronal function and in the pathogenesis of several major neuropsychiatric disorders involving the dopamine system (e.g. schizophrenia and Parkinson's disease). Little is known, however, about the effects of IL-2 on dopamine-mediated behaviors. A series of behavioral experiments were performed in mice to examine the hypothesis that species-specific IL-2 could modify behaviors known to be mediated by forebrain dopamine pathways. IL-2 administered subcutaneously produced a robust increase in locomotor activity in an elevated plus-maze. No effects of the cytokine were evident on measures of acoustic startle, prepulse inhibition of the startle response (PPI), or fearfulness. In complementary in vitro neurochemical experiments, to most closely assess physiologically relevant effects of the cytokine on dopamine release from striatal neurons, species-specific IL-2 as well as high performance liquid chromatography (HPLC) were used to measure endogenous dopamine release from striatal slices. IL-2 dose-dependently modulated veratrine-evoked release of endogenous dopamine in a biphasic pattern, increasing release at lower concentrations and inhibiting release at a high concentration of the cytokine. In radioligand competition binding experiments, IL-2 was not active at striatal binding sites for [3H]spiroperidol (D2-like receptors), [3H]mazindol binding (dopamine uptake sites) and [3H]SCH23390 (D1-like receptors), indicating that the neuromodulatory actions of IL-2 are not the result of direct or allosteric effects on dopamine receptors. Knowledge of the mechanisms by which IL-2 influences brain dopamine function could provide new insight into the pathophysiology of forebrain dopamine neurons seen in disorders such as Parkinson's disease and schizophrenia.
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PMID:Modulation of behavioral and neurochemical measures of forebrain dopamine function in mice by species-specific interleukin-2. 905 75

Dysfunction of T-cell mediated immunity, which is indicated by deficient production of interleukin-2 (IL-2) and elevated levels of the soluble interleukin-2 receptor (sIL-2R), has been consistently demonstrated in schizophrenia. Recent studies on interferon-gamma (IFN-gamma), a cytokine which is also produced by T-helper cells, have indicated a lowered production in acute schizophrenia. It is not known whether this deficit is restricted to cases of acute schizophrenia or whether it is also present in residual schizophrenia and in first degree relatives, and therefore might be associated with genetic liability to the disease. We investigated 27 individuals (schizophrenics and first degree relatives) of 6 families with multiple occurrence of schizophrenia and 27 age- and sex-matched healthy controls. The production of IFN-gamma was lowered only in the acutely ill schizophrenic individuals, when compared to both controls and first degree relatives. In the context of current knowledge, this result indicates that the production of IFN-gamma can be discussed as a marker of acute exacerbation of schizophrenia, but it is not likely to represent a phenotypic marker of a genetic trait associated with the disease.
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PMID:Production of interferon-gamma in families with multiple occurrence of schizophrenia. 907 78

Alternations in immune function have been described in a variety of psychiatric disorders including schizophrenia and depression; however, we do not know of any research involving social phobia and the immune system. This preliminary study explores the relationship between social phobia and two well-established immune parameters, serum interleukin-2 (IL-2) levels, a potent immune and central nervous system modulator, and soluble interleukin-2 receptors (SIL-2Rs), a well-known marker of T-cell activation. Fifteen subjects with generalized social phobia and 15 healthy volunteers had serum IL-2, and SIL-2Rs measured by enzyme-linked immunoassay. Subjects with social phobia and normal volunteers had similar mean serum IL-2 and SIL-2R levels. The data suggest that, unlike other psychiatric disorders, these immune measures may not be used to differentiate patients with generalized social phobia from normal volunteers.
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PMID:Serum interleukin-2 and soluble interleukin-2 receptor levels in generalized social phobia. 916 May 48


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