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)

Regional abnormalities of brain connectivity may be an important substrate for the expression of schizophrenia, a severe form of mental illness. Brain imaging and postmortem morphometric studies indicate hippocampal structure is abnormal in schizophrenia. To study molecular components of hippocampal connectivity the presynaptic proteins SNAP-25 and synaptophysin were assayed in postmortem samples. Immunocytochemical studies indicated reduced SNAP-25 immunoreactivity in schizophrenia compared to controls, particularly in the terminal fields of entorhinal cortex projections. Although there were no overall changes in synaptophysin immunoreactivity, in the granule cell layer of the dentate gyrus synaptophysin immunoreactivity was increased in schizophrenia. These results indicate that disconnection of a subset of hippocampal circuitry from the entorhinal cortex, as well as intrinsic changes in hippocampal connectivity, may contribute to the mechanism of illness in schizophrenia.
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PMID:SNAP-25 deficit and hippocampal connectivity in schizophrenia. 961 21

An impairment of prefrontal cortical functioning in schizophrenia ('hypofrontality') has been suggested by clinical, neuroimaging, and postmortem brain tissue studies. We used Western immunoblot and Northern hybridization analyses of postmortem brain tissue obtained from 14 schizophrenic patients and 12 control patients of similar ages to measure tissue levels of synaptophysin (a structural synaptic vesicle protein) and of SNAP-25 (a 25-kDa presynaptic protein), and their encoding mRNAs, in Brodmann's area 10 of prefrontal cortex. There were significant decreases in tissue levels of both of these proteins in prefrontal cortex of schizophrenic patients relative to controls. In contrast, tissue levels for the mRNAs encoding these proteins were not decreased in schizophrenic patients. Subsequent labeling of the same Western immunoblots showed no difference in tissue levels of glial fibrillary acidic protein (GFAP) in schizophrenic and control patients. Similarly, subsequent hybridization of the same Northern hybridization membranes showed no difference in tissue levels of GFAP mRNA or of 28S rRNA in schizophrenic and control patients. These alterations in tissue levels of synaptophysin and SNAP-25 are consistent with the idea that the clinically observed 'hypofrontality' of schizophrenia arises from abnormalities of synaptic number or structural integrity in prefrontal cortex.
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PMID:Alterations in synaptic proteins and their encoding mRNAs in prefrontal cortex in schizophrenia: a possible neurochemical basis for 'hypofrontality'. 1008 7

Synaptic pathology is central in the pathogenesis of several psychiatric disorders, for example in Alzheimer's disease (AD) and schizophrenia. Quantification of specific synaptic proteins has proved to be a useful method to estimate synapitc density in the brain. Using this approach, several synaptic proteins have been demonstrated to be altered in both AD and schizophrenia. Until recently, the analysis of synaptic pathology has been limited to postmortem tissue. In living subjects, these synaptic proteins may be studied through analysis of cerebrospinal fluid (CSF). In an earlier study performed by us, one synaptic vesicle specific protein, synaptotagmin, was detected in CSF for the first time using a procedure based on affinity chromatography, reversed-phase chromatography, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and chemiluminescence immunoblotting. However, other synaptic proteins were not detectable with this procedure. Therefore, we have developed a procedure including precipitation of CSF proteins with trichloroacetic acid, followed by liquid-phase isoelectric focusing using the Rotofor Cell, and finally analysis of Rotofor fractions by Western blotting for identification of synaptic proteins in CSF. Five synaptic proteins, rab3a, synaptotagmin, growth-associated protein (GAP-43), synaptosomal-associated protein (SNAP-25) and neurogranin, have been demonstrated in CSF using this method. The major advantage of liquid-phase isoelectric focusing (IEF) using the Rotofor cell is that it provides synaptic proteins from CSF in sufficient quantities for identification. This method may also be suitable for identification of other types of trace amounts of brain-specific proteins in CSF. These results demonstrate that several synaptic proteins can be identified and measured in CSF to study synaptic function and pathology in degenerative disorders.
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PMID:Identification of synaptic vesicle, pre- and postsynaptic proteins in human cerebrospinal fluid using liquid-phase isoelectric focusing. 1021 48

Research efforts to identify and understand the pathophysiology of schizophrenia and bipolar illness are limited by the inability to study neuronal tissue of living patients. An alternative to sampling brain tissue from living patients is to measure neuronal proteins found in cerebral spinal fluid. One such candidate protein is synaptosomal-associated protein 25kDa. Our hypothesis is that the level of this protein in cerebral spinal fluid may be a marker of neuronal pathology. Cerebral spinal fluid from headache, schizophrenic, bipolar, and control subjects was used to measure the SNAP-25 level by quantitative dot blotting. Schizophrenic subjects had significantly elevated levels of SNAP-25 as compared to headache and control subjects. However, there was no significant difference between the bipolar group and schizophrenic or control groups. This study reports on a potentially useful clinical marker in schizophrenia, and the presence of elevated cerebral spinal fluid SNAP-25 may indicate alterations in neuronal functioning.
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PMID:CSF SNAP-25 in schizophrenia and bipolar illness. A pilot study. 1063 77

Recent studies have suggested that synaptic abnormalities may be part of the pathophysiology of schizophrenia. SNAP-25 (synaptosomal-associated protein of 25 kD) is one of the synaptic proteins responsible for presynaptic neurotransmission, axonal elongation and synaptogenesis. Genetic variation in the 5'-upstream region of the SNAP-25 gene was analyzed in 87 unrelated schizophrenic patients and 100 healthy controls. A novel polymorphic (TAAA)(n) tandem repeat was identified in the 5'-upstream region. There were no significant differences between the patient and the control groups in the distribution of repeat numbers of alleles or genotypes. In addition, no associations were found between the polymorphism for subtypes, longitudinal courses or positive family history of the patients. Our results suggest that polymorphisms in the 5'-upstream region of the SNAP-25 gene have no association with schizophrenia.
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PMID:Polymorphism of the 5'-upstream region of the human SNAP-25 gene: an association analysis with schizophrenia. 1128 90

Linkage studies indicate that chromosome 22q contains a locus, or loci, for schizophrenia (SZ) and bipolar disorder (BPD). Furthermore, the congenital disorder velo cardio facial syndrome (VCFS), which is usually caused by a 22q11 microdeletion, is associated with an increased prevalence of psychiatric disease, including SZ and BPD. One plausible candidate gene that maps to 22q11, in a region deleted in the most common form of VCFS, is SNAP29, a member of the SNAP-25 family of SNARE proteins. To search for possible functional mutations in SNAP29 that could be analyzed as candidates for 22q11-linked psychiatric problems, exons, intron-exon junctions and the promoter region were screened. No coding variants were found, although a silent mutation at codon 6 and three single nucleotide polymorphisms (SNPs) were identified in the 5' untranslated and promoter regions. One SNP, an A-->G transition 923 [corrected] nucleotides upstream of the transcription start site, showed a moderately significant difference in the distribution of alleles and genotypes in patients with SZ compared with controls (allele frequency: chi(2) = 5.57, 1 df, P = 0.018; genotype: chi(2) = 9.49, 2 df, P = 0.009; odds ratio = 1.59, 95% Cl = 1.08--2.34). No significant difference was found in patients with BPD. Although the functional significance of this mutation is not known, the tetranucleotide core sequence of the ets and IK2 families of transcription factors is altered as a result of the SNP. These data suggest that a mutation in the SNAP29 gene promoter region, or a mutation in linkage disequilibrium with the promoter SNP, may be involved in the pathogenesis of chromosome 22-linked SZ.
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PMID:Polymorphism in SNAP29 gene promoter region associated with schizophrenia. 1131 22

SNAP-25 levels were measured in ventral hippocampus in subjects with unipolar depression (n = 12), bipolar disorder (n = 13), schizophrenia (n = 15) and controls (n = 15) using quantitative immunocytochemistry. SNAP-25 levels were reduced significantly in stratum oriens of bipolar patients compared with controls (p < 0.05); they were also reduced significantly in st. oriens (p < 0.01 vs schizophrenia), in alveous (p < 0.01 vs schizophrenia) and in presubiculum (p < 0.05 vs depressed). SNAP-25 levels were also reduced in several layers of schizophrenics, only significantly so in st. granulosum (p < 0.05 vs controls). In contrast, depressed SNAP-25 levels increased in st. moleculare (p < 0.01 vs schizophrenics) and presubiculum (p < 0.05 vs controls and bipolars; p < 0.01 vs schizophrenics). SNAP-25 values were not affected by age, sex, race, post-mortem interval, brain pH, side of brain, age of onset of disease, family history of psychiatric disease, drug or alcohol use, antipsychotic drug treatment, or mode of death. The reported changes in SNAP-25 levels appear to be disease specific, separating synaptic pathology in unipolar depression from that observed in schizophrenia and bipolar disorders.
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PMID:Altered levels of the synaptosomal associated protein SNAP-25 in hippocampus of subjects with mood disorders and schizophrenia. 1171 67

The pathobiology of schizophrenia is poorly understood, and many neuroanatomical domains have been considered to underlie the pathophysiology of the disease. There is considerable clinical and neuroradiological evidence to support cerebellar involvement in the schizophrenic illness. We have analysed the changes in synaptic and cytoskeletal proteins in the cerebellum associated with schizophrenia. The cerebellar expression of tau and MAP2 proteins is similar in schizophrenia to that detected in age-matched controls, whereas the level of SNAP-25 is significantly depleted in the schizophrenic cerebellum. Other synaptic proteins, such as synaptophysin and syntaxin, are not affected. This provides evidence that alterations of the cerebellar synaptic network occur in schizophrenia. These changes may influence cerebellar-forebrain connections, especially those with the frontal lobes, and give rise to the cognitive dysmetria that is characteristic of the clinical phenotype in schizophrenia.
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PMID:Loss of synaptic but not cytoskeletal proteins in the cerebellum of chronic schizophrenics. 1175 64

A fundamental molecular component of neural connectivity is the SNARE (SNAP receptor) protein complex, which consists of three proteins, syntaxin, SNAP-25 and VAMP. Under appropriate conditions, the SNARE complex can be formed in vitro. To investigate the hypothesis that dysregulation of SNARE proteins or their interactions could be abnormal in severe mental disorders, the three SNARE proteins and the complex were studied in post-mortem anterior frontal cortex homogenates. An ELISA was used to quantify SNARE protein immunoreactivities in cortical homogenates from four groups: patients with schizophrenia who died of causes other than suicide (n = 6), patients with schizophrenia and suicide (n = 7), patients with depression and suicide (n = 11), and controls (n = 11). Differences between groups in patterns of SNARE protein immuno-reactivities were demonstrated [Wilks' Lambda F(9,68) = 3.57, P = 0.001]. Protein-by-protein analyses indicated a significant reduction in SNAP-25 immunoreactivity in the schizophrenia non-suicide group [28% decrease relative to controls, F(3,31) = 6.45, P = 0.002, Student-Newman-Keuls test, P < 0.01]. The intercorrelations between SNARE protein and synaptophysin immunoreactivities were high in controls, but lower in the other groups, further indicating disturbances in relationships between these proteins. The extent of SNARE complex formation in vitro was studied using immuno-blotting. Significant differences related to group membership were observed for the SNARE complexes identified by SNAP-25 [Wilks' Lambda F(3,31) = 4.76, P = 0.008] and by syntaxin immunostaining [Wilks' Lambda F(3,31) = 9.16, P = 0.0002]. In both groups with suicide as a cause of death, relatively more SNAP-25 and syntaxin was present in the heterotrimeric SNARE complex than in other molecular forms. These abnormalities in the SNARE complex could represent a molecular substrate for abnormalities of neural connectivity in severe mental disorders.
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PMID:Abnormalities of SNARE mechanism proteins in anterior frontal cortex in severe mental illness. 1188 50

Recent imaging and postmortem studies suggest that impaired connectivity is involved in the pathophysiology of schizophrenia and major affective disorders. We investigated the presynaptic proteins complexin (Cx) I and Cx II in postmortem prefrontal cortex in schizophrenia (n = 13; six suicide, seven nonsuicide), major depression (n= 11, all suicide) and controls (n = 11) with an enzyme-linked immunoadsorbent assay (ELISA). Overall analysis indicated a significant difference between groups (F = 3.93, P = 0.007). Cx I (enriched in inhibitory terminals) was decreased 33% in schizophrenia (26% in schizophrenia/nonsuicide, 42% in schizophrenia/suicide) and 27% in major depression. Cx II (enriched in excitatory terminals) was not significantly different. Analysis of the ratio of Cx II/Cx I was carried out as an indication of the balance of excitatory to inhibitory terminals. A significant difference between groups (ANOVA, F = 6.42, P = 0.005) was observed. The mean value of Cx II/Cx I was significantly increased by 34% in schizophrenia (26% in schizophrenia/nonsuicide and 43% in schizophrenia/suicide) and by 32% in depression compared with control (Student-Newman-Keuls test, P = 0.05). Immunoreactivities of the two complexins were highly correlated in all groups. However, compared with controls and depression, samples from cases with schizophrenia appeared to have relatively less Cx I for similar amounts of Cx II. Immunocytochemical studies of rat frontal cortex after 3 weeks treatment with chlorpromazine, trifluoperazine or haloperidol revealed no differences in complexins, synaptophysin, SNAP-25, syntaxin or VAMP in comparison with animals treated with vehicle. Alterations of complexins may contribute to the molecular substrate for abnormalities of neural connectivity in severe mental disorders.
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PMID:Altered immunoreactivity of complexin protein in prefrontal cortex in severe mental illness. 1208 66


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