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)

The authors examined 29 patients with endogenous psychosis (incl. 25 suffering from paranoid schizophrenia and four suffering from bipolar psychosis diagnosed according to DSM III criteria) with the aim to reveal the relationship of hitherto little studied HLA-DR antigens and the psychotic disease. Moreover, the passesed in the group also the ration of HLA-A, B, C antigens. In patients with paranoid schizophrenia and in all patients they found a higher incidence of HLA-DR2 antigens and a lower incidence of HLA-DRw6 and DR7. A statistically significant result was obtained only for HLA-DR2, and only before correction of p. The corrected p value (for the number of antigens) was no longer significant. This finding may serve as a stimulus to resolve the relationship of HLA-DR antigens and schizophrenia in a larger number of patients and in a greater number of departments.
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PMID:[Incidence of HLA-DR antigens in endogenous psychoses]. 280 19

A number of assays were performed to assess immunologic function in 28 patients with clinically well-defined schizophrenia. Our data provide laboratory evidence that patients with schizophrenia have characteristics consistent with an autoimmune process, directed to components of the brain, which may participate in either the pathogenesis or etiology of schizophrenia. One-third of our patients had a clinically evident autoimmune syndrome unrelated to their psychiatric illness. Of the nine patients with an autoimmune disease, two had one autoantibody in their serum and five had more than one autoantibodies. Twelve of eighteen patients without clinical evidence of autoimmune disease had no detectable autoantibodies. Mitogenic responses to PHA and PWM were significantly reduced in the patient population when compared to controls. Fifty percent of the patients had an increased percentage (greater than 5%) of blood-borne HLA-DR (+) OKT4 (+) T-helper lymphocytes. Immune reactivity toward brain antigens was sought by measuring lymphocyte transformation to a saline extract of frontal lobe, and by immunoblotting of antigens extracted from frontal lobe, cingulate gyrus, interventricular septum, and hippocampus. Lymphocyte transformation did not reveal differences between patient and control groups. Normal sera were found to contain antibody to some of these brain antigens. However, patients with schizophrenia had antibody to antigens of the hippocampus, septal region and cingulate gyrus which were not encountered during analysis of normal sera.
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PMID:Clinical and laboratory evidence of autoimmunity in acute schizophrenia. 347 98

An association of HLA-DR8 and DR1 with DSM-III schizophrenia has been reported in Japan (Miyanaga et al. (1984) Biol. Psychiatr. 19, 121-129). To further investigate this preliminary finding, we compared HLA-DR types in 44 unrelated Japanese schizophrenics (DSM-III-R) with those in 51 unrelated, healthy Japanese volunteers. Group-specific PCR amplification was used in the determination of HLA-DR in the patients. No significant difference was observed in the frequency of any DR types between patients and controls, after statistical correction for multiple testing. However, the frequency of DR1 in our patients (23%) and controls (10%) was almost the same as those in the previous report (22% vs. 10%), which means that there is a suggestive trend which could become significant if numbers were larger. It is argued that an exact determination of HLA-DR by DNA typing is important in current HLA studies of schizophrenia.
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PMID:HLA-DR types in Japanese schizophrenics: analysis by group-specific PCR amplification. 789 26

The frequencies of HLA class I (HLA-A, B, C) and class II (HLA-DR, DQ) antigens were measured in 107 unrelated schizophrenic subjects and the results compared with 264 controls from south-east Scotland and a second control group of 133 individuals from north-east England. The expression of HLA-B35 was significantly reduced in the schizophrenic population compared to both control populations and these differences remained significant after correction for multiple testing. Linkage of schizophrenia and the major histocompatibility complex region of chromosome 6p was, however, excluded in a group of 17 families multiply affected with schizophrenia. Linkage was also excluded with several red cell antigens, red cell enzymes and plasma proteins. A negative association between the frequency of an HLA antigen and schizophrenia suggests that immune mechanisms may contribute to the aetiology of the disease in some subjects.
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PMID:Reduced expression of HLA-B35 in schizophrenia. 884 Mar 90

By using phase-contrast microscopy combined with a fluorescent staining technique, the frequency of blast-type atypical lymphocytes (BTALs) appearing in peripheral blood and the phenotypic expression of their surface antigens were studied in 24 patients with schizophrenia, 16 with mood disorder and 14 healthy controls. BTALs were classified as being stimulated or activated cells, morphologically characterized by their large size, dark cytoplasm, a hollow perinuclear containing a few granules and finely dispersed chromatin structures with a few evident nucleoli. A significantly higher number of BTALs were found in the schizophrenic patients compared with healthy control subjects or patients with mood disorder. Further, there was a significant difference in the frequency of BTALs between patients with mood disorder and healthy control subjects. No significant difference in the frequency of BTALs was found between the schizophrenic patients with and without medication. Immunostaining of BTALs revealed that these cells consisted of B, T and non-B, non-T cell subpopulations. Contrary to our expectations, the T cell was only one third of the BTAL population. HLA-DR and CD38 were expressed on most BTALs (> 70%), while CD25, an early activation marker of T cells was rarely found on BTALs (< 0.3%). The differences in activated lymphocyte populations which appeared as morphologically atypical in the circulation among some psychiatric patients and infectious or autoimmune diseases are discussed. This is the first report on populations of BTALs.
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PMID:Immunophenotypic studies on atypical lymphocytes in psychiatric patients. 954 Nov 46

Activation of microglia/macrophages is a key event in response to pathological changes in the CNS. HLA-DR is a valuable immunohistochemical marker that specifically reacts with activated microglia cells. In order to elucidate a potential role of microgliosis in severe psychiatric illnesses, post-mortem frontal cortex and hippocampus of patients with schizophrenia (n = 14) and affective disorder (n = 6) and control specimens (n = 13) were studied. Additionally Alzheimer's disease cases (n = 8) were included as a human model system with typical neurodegenerative alterations and microglia activation. All patient groups revealed subjects with abundant microglia immunostaining (schizophrenia, three patients; affective disorder, one patient; Alzheimer's disease, four patients) in both gray and white matter. This finding provides evidence for distinct neuropathological changes in brains of patients with schizophrenia and affective disorder. The activation of microglia cells, which represent a major part of the brain immune response, may help to unravel the pathophysiological processes in severe psychiatric illnesses.
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PMID:Evidence for activation of microglia in patients with psychiatric illnesses. 1047 18

Glia play a major role in neuronal migration, synapse formation, and control of neurotransmission in the developing and mature nervous system. This study investigated whether chronic schizophrenia is associated with glial changes in 3 regions of the cerebral cortex: dorsolateral prefrontal cortex (Brodmann's area 9), the superior temporal gyrus (area 22), and the anterior cingulate gyrus (area 24). In a blind study, astroglia and microglia were identified immunocytochemically in frozen sections from postmortem schizophrenic and control brains. Astroglia and microglia were identified using antibodies to glial fibrillary acidic protein (GFAP) and class II human leucocyte antigen (HLA-DR) respectively. They were then quantified for each cortical layer. Significant differences were found in HLA-DR+ microglial numerical density in 2 of the areas. A 28% increase (p < 0.05) was found in area 9 in 8 schizophrenics (115 +/- 9 cells/mm2) compared with 10 controls (89 +/- 5 cells/mm2), when combining all cortical layers and both cerebral hemispheres. For area 22, there was a 57% increase (p < 0.01) in microglia in 7 schizophrenics (139 +/- 6 cells/mm2) compared with 10 controls (88 +/- 5 cells/mm2). In area 24 the same trend was evident, but the results did not reach significance. Microglial number was further analyzed for each cortical layer, which confirmed the overall pattern. For all areas, numerical density of astroglia showed no significant differences between schizophrenics and controls. Cortical thickness was measured in all areas and total neuronal numerical density was estimated for area 22. Again, no significant differences were found between schizophrenics and controls. This study demonstrates a specific increase in the numerical density of HLA-DR+ microglia in temporal and frontal cortex of chronic schizophrenics, not related to aging, which might be implicated in possible changes in cortical neuropil architecture in schizophrenia.
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PMID:Increase in HLA-DR immunoreactive microglia in frontal and temporal cortex of chronic schizophrenics. 1074 3

The existence of atypical lymphocytes with specific morphological characteristics in the peripheral blood of schizophrenic patients has been suggested in several reports over the last 40 years. In our study this observation was examined not only by using the formerly applied method of light microscopy for general cell distribution and lymphocyte morphology but also by applying flow cytometry, a well established immunological method for lymphocyte patterns such as lymphocyte subgroups and lymphocyte activity. In contrast to the previously published data, our results demonstrated no differences in cell distribution (lymphocytes, polymorphonuclear cells, eosinophil and basophil granulocytes, monocytes), lymphocyte morphology ("atypical lymphocytes" vs. "normal lymphocytes"), distribution of lymphocyte-subtypes (T-cells (CD3(+)), T-helper-cells (CD3(+)/CD4(+)), cytotoxic T-cells (CD3(+)/CD8(+)), B-cells (CD19(+)), NK-cells (CD3(-)/CD56(+))) or state of T-lymphocyte activity (CD25(+) or HLA-DR(+)-cells) in schizophrenic patients compared to healthy controls. We suggest that possible immunological alterations in schizophrenia do not correlate with morphological characteristics of lymphocytes observable by light microscopy or an altered state activity of T-lymphocytes examined by flow cytometric parameters. Further studies should concentrate on intracellular and functional aspects of the different lymphocyte subgroups.
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PMID:Search for atypical lymphocytes in schizophrenia. 1504 33

Immunological alterations have been demonstrated in peripheral blood and cerebrospinal fluid of patients with schizophrenia, while previous postmortem studies have provided an inconsistent picture as to the role of microglia in the context of schizophrenia. Microglial activation is a sensitive indicator of changes in the CNS microenvironment, such as inflammatory and neurodegenerative processes. The aim of the present postmortem study was to examine HLA class II (HLA-DR) expression on microglia in brain regions which are particularly relevant for schizophrenia, with regard to hemispheric lateralization. Dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), hippocampus and mediodorsal thalamus (MD) were studied in 16 cases with schizophrenia and 16 control subjects. Immunostaining was found in all brain regions and was not restricted to macrophage-like ameboid cells, but also appeared in ramified cells. Region-specific HLA-DR-positive cell density was not significantly different between cases with schizophrenia and controls. However, ameboid microglial cells were lateralized towards the right hemisphere in healthy subjects but not in the schizophrenia group (P=0.01). Postmortem interval correlated with ramified cell numbers in ACC/DLPFC (P=0.01/0.04) and ameboid cell density in hippocampus (P=0.03). Age, gender, duration of disease, medication dosage, storage delay and whole brain volume had no effect. Single case analysis revealed highly elevated microglial cell numbers in ACC and MD of two schizophrenic patients who had committed suicide during acute psychosis. In conclusion, the present data suggest the absence of microgliosis but decreased cerebral lateralization of ameboid microglia in schizophrenia.
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PMID:Distribution of HLA-DR-positive microglia in schizophrenia reflects impaired cerebral lateralization. 1678 54

Schizophrenia probably has a developmental origin. This review refers to three of our published series of studies related to this hypothesis: loss of dendritic spines on cerebral neocortical pyramidal neurons, decreased numerical density of glutamatergic neurons, and microgliosis. First, brains of schizophrenic patients and non-schizophrenic controls were obtained post mortem and blocks of multiple cortical areas impregnated with a Rapid Golgi method. Spines were counted on the dendrites of pyramidal neurons of which the soma was in layer III (which takes part in corticocortical connectivity) and which met strict criteria for impregnation quality. Data were obtained blind: diagnoses were only revealed by a third party after measurements were completed. The mean spine count in all cortical areas studied in the control series was 243 mm(-1) of dendrite and in the schizophrenics 108. Measurements in frontal and temporal association cortex showed the greatest reduction in spine number in schizophrenia (299 in control frontal cortex and 101 in schizophrenics, and 276 mm(-1) in control temporal cortex and 125 in schizophrenics). There was no correlation of spine loss with age at death. Our results support the concept of a neurodevelopmental defect in the neuropil affecting glutamatergic neurons in schizophrenia and may help to explain loss of cortical volume without loss of neurons. In a second part of our study we used an antibody to the kainate receptor subunit GluR 5/6/7 and showed a decrease in numerical density of presumed glutamatergic neurons in schizophrenic orbitofrontal cortex. Finally, as glia play a major role in the developing nervous system, we investigated whether schizophrenia was associated with glial changes in frontal and temporal cortex. Astroglia and microglia were identified in schizophrenic and control brains, using antibodies to glial fibrillary acidic protein (GFAP) and class II human leucocyte antigen (HLA-DR), respectively. Significant increases were found in microglial numerical density in schizophrenics compared with controls: 28% in frontal area 9 (115 cells mm(-2) compared with 89), and a 57% increase in temporal area 22 (139 cells mm(-2) compared with 88). For both areas, astroglia showed no significant differences between schizophrenics and controls. No significant differences were found in cortical thickness or total neuronal numerical density between the two groups. This specific increase in numerical density of microglia in temporal and frontal cortex of chronic schizophrenics, not related to aging, could be related to possible changes in cortical neuropil architecture as revealed by loss of dendritic spines.
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PMID:When cortical development goes wrong: schizophrenia as a neurodevelopmental disease of microcircuits. 2040 6


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