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)

Post-mortem brain tissue was obtained from 28 patients with brain disorders, of which 15 had clinically diagnosed schizophrenia, 6 Alzheimer type dementia, 5 dementia with tangles and 2 cases of Down's syndrome. The controls were 22 cases from autopsies without brain disorders or with no known episodes of brain disorder. The tissues were stained for the detection of carbohydrate deposits in the hippocampal formation, using lectin, immunohistochemical and conventional staining methods. The staining revealed the existence of spherical deposits in the inner and middle molecular layers of the dentate gyrus in the hippocampal formation which contained fucose, galactose, N-acetyl galactosamine, N-acetyl glucosamine, sialic acid, mannose and chondroitin sulfate. The number of the deposits was higher in patients with brain disorder such as schizophrenia, Alzheimer type dementia, dementia with tangles or Down's syndrome, and in some aged individuals, in comparison to those in younger individuals. No deposits were detected in a few younger or aged individuals. Spherical deposits 3-10 microm in diameter may be an immature form of the corpora amylacea, since they were similar in the histochemical characteristics with lectin, immunohistochemical and conventional staining methods. However, differing staining ability by hematoxylin, periodic acid Schiff's reagent and antibodies against the intracellular degraded proteins such as ubiquitin and tau-protein was observed. The antibodies against ubiquitin and tau-protein showed clear reactivity with the corpora amylacea and no reactivity with spherical deposits, indicating that the corpora amylacea has an intracellular origin and spherical deposits an extracellular matrix origin. The results obtained in this study indicate that not only neuronal degeneration but also unusual glycometabolism in neurons may disturb the neuronal function and cause brain disorders, and that spherical deposits may cause dysfunction of the neuronal network in the dentate gyrus of the hippocampus which is closely linked with recognition and memory functions.
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PMID:The carbohydrate deposits detected by histochemical methods in the molecular layer of the dentate gyrus in the hippocampal formation of patients with schizophrenia, Down's syndrome and dementia, and aged person. 1144 83

Schizophrenia is a chronic, severely disabling brain disorder with symptomatic onset in early adulthood. Typical antipsychotic medications that block dopamine D2 receptors are most effective in treating the psychosis but have limited effects on the negative symptoms and cognitive impairments. Considerable research has demonstrated that noncompetitive NMDA receptor antagonists, the dissociative anaesthetic like phencyclidine and ketamine, reproduce the cardinal symptomatic features of schizophrenia. Postmortem studies reveal variable alterations in glutamate receptors and their modulators in schizophrenia. Several clinical trials indicate agents that enhance NMDA receptor function via the glycine modulatory site reduce negative and variably improve cognitive function in schizophrenics receiving typical antipsychotics. Thus, hypofunction of a subpopulation of cortico-limbic NMDA receptors may participate in the pathophysiology of schizophrenia.
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PMID:Glutamatergic mechanisms in schizophrenia. 1180 69

Schizophrenia is a major mental disorder, characterized by their set of symptoms, including hallucinatory-delusional symptoms, thought disorder, emotional flattening, and social withdrawal. Since 1980s, advances in neuroimaging and neurophysiological techniques have provided tremendous merits for investigations into schizophrenia as a brain disorder. In this article, we first overviewed neuroanatomical studies using structural magnetic resonance imaging (s-MRI), MR spectroscopy (MRS), and postmortem brains, followed by neurophysiological studies using event-related potentials (ERPs) and magnetoencephalography (MEG), in patients with schizophrenia. Evidences from these studies suggest that schizophrenia is a chronic brain disorder, structurally and functionally affecting various cortical and subcortical regions involved in cognitive, emotional, and motivational aspects of human behavior. Second, we reviewed recent investigations into neurobiological basis for schizophrenic symptoms (auditory hallucinations and thought disorder) using these indices as well as hemodynamic assessments such as positron emission tomography (PET) and functional MRI (f-MRI). Finally, we addressed the issue of the heterogeneity of schizophrenia from the neurobiological perspective, in relation to the neuroanatomical and neurophysiological measures.
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PMID:Neuroanatomy and neurophysiology in schizophrenia. 1206 45

BACKGROUND: Being born in winter and spring is considered one of the most robust epidemiological risk factors for schizophrenia. The aetiology and exact timing of this birth excess, however, has remained elusive so far. Since during phylogeny, Borrelia DNA has led to multiple germ-line mutations within the CB1 candidate gene for schizophrenia, a meta analysis has been performed of all papers on schizophrenic birth excesses with no less than 3000 cases each. All published numerical data were then plotted against the seasonal distributions of Ixodes ticks worldwide. RESULTS: In the United States, Europe and Japan the birth excesses of those individuals who later in life develop schizophrenia mirror the seasonal distribution of Ixodes ticks nine months earlier at the time of conception. South of the Wallace Line, which limits the spread of Ixodes ticks and Borrelia burgdorferi into Australia, seasonal trends are less significant, and in Singapore, being non-endemic for Ixodes ticks and Lyme disease, schizophrenic birth excesses are absent. CONCLUSION: At present, it cannot be excluded that prenatal infection by B. burgdorferi is harmful to the implanting human blastocyst. The epidemiological clustering of sporadic schizophrenia by season and locality rather emphasises the risk to the unborn of developing a congenital, yet preventable brain disorder later in life.
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PMID:Seasonal correlation of sporadic schizophrenia to Ixodes ticks and Lyme borreliosis. 1245 16

Schizophrenia is a disorder characterized by multiple symptoms, with a varied course and outcome. The etiology is yet unknown, but multiple pathological processes or, equally likely, a unique pathophysiological process, may be involved. Here, we review evidence for progressive changes in schizophrenia in order to understand further the pathophysiology of this disorder. We first present evidence for clinical and psycho-social changes over time, followed by evidence from structural brain studies that suggests that schizophrenia is a brain disorder. We then review findings from the small number of longitudinal studies that have evaluated structural brain changes in schizophrenia, followed by a review of the evidence for neurophysiological changes, both cross-sectional and longitudinal. This is followed by a discussion of possible cellular mechanisms, including NMDA receptor abnormalities, that might account for structural and functional brain changes (temporal and frontal), and we discuss how these abnormalities might be related to not only the specific signs and symptoms of schizophrenia but also to the onset and course of the illness. Finally, we discuss neurodevelopment (static and perhaps non-static alterations) and neurodegenerative theories of schizophrenia. We propose that the two are not mutually exclusive, but instead likely reflect a "two-hit" model for some subtypes of schizophrenia.
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PMID:Progressive changes in schizophrenia: do they exist and what do they mean? 1267 13

Schizophrenia and its subtypes are part of a complex brain disorder with multiple postulated aetiologies. There is evidence that this common disease is genetically heterogeneous, with many loci involved. In this report, we describe a mother and daughter affected with schizophrenia, who are carriers of a t(9;14)(q34;q13) chromosome. By mapping on flow sorted aberrant chromosomes isolated from lymphoblast cell lines, both subjects were found to have a translocation breakpoint junction between the markers D14S730 and D14S70, a 683 kb interval on chromosome 14q13. This interval was found to contain the neuronal PAS3 gene (NPAS3), by annotating the genomic sequence for ESTs and performing RACE and cDNA library screenings. The NPAS3 gene was characterised with respect to the genomic structure, human expression profile, and protein cellular localisation to gain insight into gene function. The translocation breakpoint junction lies within the third intron of NPAS3, resulting in the disruption of the coding potential. The fact that the bHLH and PAS domains are disrupted from the remaining parts of the encoded protein suggests that the DNA binding and dimerisation functions of this protein are destroyed. The daughter (proband), who is more severely affected, has an additional microdeletion in the second intron of NPAS3. On chromosome 9q34, the translocation breakpoint junction was defined between D9S752 and D9S972 and no genes were found to be disrupted. We propose that haploinsufficiency of NPAS3 contributes to the cause of mental illness in this family.
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PMID:Disruption of the neuronal PAS3 gene in a family affected with schizophrenia. 1274 93

Traditionally, the diagnosis of schizophrenia has depended on the presence of specific behavioral phenomena assessed by way of behavioral observation and patient symptomatic report. Even though the introduction of explicit diagnostic criteria and structured interviews has improved the reliability of schizophrenia diagnosis, it is still unclear how best to define schizophrenia in order to further etiologic research. This situation persists despite ample evidence that schizophrenia is a heritable brain disorder and the existence of laboratory measures that tap into this neurobiological genetic diathesis. We contend that such laboratory measures can be used to supplement traditional clinical assessment in order to improve the definition of schizophrenia, thereby enhancing research into schizophrenia's origins. Ultimately, this increased understanding of the disorder's etiology should facilitate the development of targeted therapeutic interventions.
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PMID:At issue: assessment of schizophrenia: getting closer to the cause. 1460 36

The mediodorsal thalamic nucleus (MD) is the principal relay nucleus for the prefrontal cortex, a brain region thought to be dysfunctional in schizophrenia. Several, but not all, postmortem studies of the MD in schizophrenia have reported decreased volume and total neuronal number. However, it is not clear whether the findings are specific for schizophrenia nor is it known which subtypes of thalamic neurons are affected. We studied the left MD in 11 subjects with schizophrenia, 9 control subjects, and 12 subjects with mood disorders. Based on morphological criteria, we divided the neurons into two subclasses, presumably corresponding to projection neurons and local circuit neurons. We estimated MD volume and the neuron number of each subclass using methods based on modern unbiased stereological principles. We also estimated the somal volumes of each subclass using a robust, but biased, approach. In addition, we investigated the left MD in four cynomolgus monkeys chronically exposed to haloperidol and in four control monkeys in order to assess the possible effects of antipsychotic medications. The three human subject groups did not differ in any of the measures. In addition, no differences were observed between the two groups of monkeys. Thus, these findings do not support the hypothesis that the MD is a locus of pathology in schizophrenia, although they cannot rule out important functional or structural changes in parameters not measured. Like other studies, this investigation is subject to the limitations involved in sampling from a heterogeneous population emphasizing the need to continue to improve the application of robust, unbiased techniques to quantitative studies of this complex brain disorder.
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PMID:Stereological analysis of the mediodorsal thalamic nucleus in schizophrenia: volume, neuron number, and cell types. 1506 19

The discovery of the pathophysiology(ies) for schizophrenia is necessary to direct rational treatment directions for this brain disorder. Firm knowledge about this illness is limited to areas of phenomenology, clinical electrophysiology, and genetic risk; some aspects of dopamine pharmacology, cognitive symptoms, and risk genes are known. Basic questions remain about diagnostic heterogeneity, tissue neurochemistry, and in vivo brain function. It is an illness ripe for molecular characterization using a rational approach with a confirmatory strategy; drug discovery based on knowledge is the only way to advance fully effective treatments. This paper reviews the status of general knowledge in this area and proposes an approach to discovery, including identifying brain regions of dysfunction and subsequent localized, hypothesis-driven molecular screening.
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PMID:Phenotype of schizophrenia: a review and formulation. 1534 Mar 52

Based upon pharmacological challenge and postmortem studies, schizophrenia has been hypothesized to be caused by decreased glutamatergic neurotransmission. We investigated the glutamatergic neuronal metabolism of the dorsolateral prefrontal cortex with localized 1H magnetic resonance spectroscopy in 18 first-episode patients, 21 chronic patients with schizophrenia, and 21 age-matched controls. Chronic patients had significantly lower levels of glutamate/glutamine (Glx) and N-acetylaspartate (NAA) compared to healthy controls and first-episode patients. Reduced metabolite levels were not correlated with duration of illness or medication. Our results indicate glutamatergic dysfunction in chronic schizophrenia that could be evidence of a progressive brain disorder.
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PMID:Evidence for glutamatergic neuronal dysfunction in the prefrontal cortex in chronic but not in first-episode patients with schizophrenia: a proton magnetic resonance spectroscopy study. 1565 58


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