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)

We have measured the amount of Gi (the inhibitory G-protein) or Go (a similar G-protein of unknown function) in 5 areas of the medial temporal lobe of control and schizophrenic brains utilizing pertussis toxin-catalyzed ADP ribosylation. The material used has previously been shown to have asymmetrical structural abnormalities of the ventricular system. The amount of Gi or Go was reduced on the left side in the hippocampus, amygdala and parahippocampal gyrus, the difference reaching significance in the hippocampus. This data is the first report of a neurochemical correlate of the structural change in the brains of patients with schizophrenia. Decreased Gi or Go in hippocampus may relate to other reported neurochemical deficits or other transmembrane signalling abnormalities. Further investigations of these indices of secondary messenger function in relation to structural changes are indicated.
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PMID:G proteins (Gi, Go) in the medial temporal lobe in schizophrenia: preliminary report of a neurochemical correlate of structural change. 190 40

We studied the distribution of puromycin-sensitive aminopeptidase (PSA) in well-defined human brain ares by Western immunoblot in an attempt to examine its possible role in schizophrenia. The schizophrenic brains were from suicide victims (n = 13) of either sex, with an age range of 30-60 yr (average 45). The controls were mostly victims of myocardial infarction (n = 12), of either sex and between 32 and 56 yr old (average 44). The brain regions were obtained within 48 h after death. After ultracentrifugation the PSA was quantified by Western blot analysis using a PSA antiserum. The distribution of the two most abundant antigens, MW 100 kDa (PSA-100) and 170 kDA (PSA-170), were compared. PSA-100 had peptidase activity, PSA-170 did not. PSA-100 was found in all of the region studied. In the control brain areas prefrontal cingulate and frontal cortices, thalamus, hippocampus, hypothalamus and outer globus pallidus contained significantly more PSA-100 than the corresponding areas from schizophrenic brain. PSA-170 was mostly found only in areas of schizophrenic brains. In three control brains, in one area of each, it could be detected, but the level in each of these regions was less than 30% of that in the corresponding schizophrenic area. PSA-170 was found in all the schizophrenic brains, in 20 of the 35 regions we studied, with parahippocampal cortex the highest (134 ng/g wet tissue) and frontal inferior cortex the lowest (9.3 ng/g wet tissue). It was not detectable in cerebral or cerebellar white matter. Our data show that the amounts and distribution of PSA-170, a protein of unknown function, is restricted mostly to schizophrenic brain areas. The difference is not due either to neuroleptic treatment of the patient or to the postmortem proteolysis of the brain samples.
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PMID:Changes in puromycin-sensitive aminopeptidases in postmortem schizophrenic brain regions. 884 44

A balanced t(1;11)(q42.1;q14.3) translocation segregates with schizophrenia and related mental illness in a single large Scottish pedigree. We have constructed a long-range restriction map covering at least 3 Mb of the chromosome 11 breakpoint region and conducted searches for genes whose expression could be altered by the translocation, resulting in schizophrenia. Novel transcribed sequences of unknown function clustered around putative CpG islands, located approximately 500 kb and 700 kb above the breakpoint, represent the only evidence to date for expressed genes within the mapped region.
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PMID:A long-range restriction map across 3 Mb of the chromosome 11 breakpoint region of a translocation linked to schizophrenia: localization of the breakpoint and the search for neighbouring genes. 980 Feb 19

Human chromosome Xp11.3-Xp11.23 encompasses the map location for a growing number of diseases with a genetic basis or genetic component. These include several eye disorders, syndromic and nonsyndromic forms of X-linked mental retardation (XLMR), X-linked neuromuscular diseases and susceptibility loci for schizophrenia, type 1 diabetes, and Graves' disease. We have constructed an approximately 2.7-Mb high-resolution physical map extending from DXS8026 to ELK1, corresponding to a genetic distance of approximately 5.5 cM. A combination of chromosome walking and sequence-tagged site (STS)-content mapping resulted in an integrated framework and transcript map, precisely positioning 10 polymorphic microsatellites (one of which is novel), 16 ESTs, and 12 known genes (RP2, PCTK1, UHX1, UBE1, RBM10, ZNF157, SYN1, ARAF1, TIMP1, PFC, ELK1, UXT). The composite map is currently anchored with 89 STSs to give an average resolution of approximately 1 STS every 30 kb. By a combination of EST database searches and in silico detection of UniGene clusters within genomic sequence generated from this template map, we have mapped several novel genes within this interval: a Na+/H+ exchanger (SLC9A7), at least two zincfinger transcription factors (KIAA0215 and Hs.68318), carbohydrate sulfotransferase-7 (CHST7), regucalcin (RGN), inactivation-escape-1 (INE1), the human ortholog of mouse neuronal protein 15.6, and four putative novel genes. Further genomic analysis enabled annotation of the sequence interval with 20 predicted pseudogenes and 21 UniGene clusters of unknown function. The combined PAC/BAC transcript map and YAC scaffold presented here clarifies previously conflicting data for markers and genes within the Xp11.3-Xp11.23 interval and provides a powerful integrated resource for functional characterization of this clonally unstable, yet gene-rich and clinically significant region of proximal Xp.
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PMID:An integrated, functionally annotated gene map of the DXS8026-ELK1 interval on human Xp11.3-Xp11.23: potential hotspot for neurogenetic disorders. 1194 89

Two recent association studies have implicated the neuregulin-1 gene (NRG1) at chromosome 8p21-22 as a susceptibility gene for schizophrenia. Stefansson et al identified three 'at-risk' haplotypes (HapA, B and C) which spanned the NRG1 locus and shared a common core haplotype. Subsequently, they demonstrated evidence that the core haplotype was associated with schizophrenia in an independent Scottish sample. To confirm and refine this haplotype we investigated the NRG1 locus in an independent Irish case-control sample. We did not find the core haplotype to be associated in our sample. However, we identified a refined 2-marker haplotype (HapB(IRE)) that shared common alleles with one of the Icelandic 'at-risk' haplotypes and is in significant excess in the Irish cases (19.4%) vs controls (12.3%) (P=0.013). This refined 'at-risk' haplotype is also in significant excess in the Scottish case sample (17.0% vs 13.5%; P=0.036). Interestingly, this refined 'at-risk' haplotype is positioned close to an EST cluster of unknown function (Hs.97362) within intron 1 of NRG1.
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PMID:Confirmation and refinement of an 'at-risk' haplotype for schizophrenia suggests the EST cluster, Hs.97362, as a potential susceptibility gene at the Neuregulin-1 locus. 1496 80

The pericentromeric region of chromosome 18, especially 18p11.2, is described as a schizophrenia susceptibility locus. We had previously cloned two novel brain-derived transcripts from this region: the gene for a second human myo-inositol monophosphatase (IMPA2) and a gene of unknown function, C18orf1. Recently, we reported a distortion of transmission of the tandem repeat marker D18S852, embedded in the 3'-untranslated region of C18orf1, in schizophrenia, using a family-based association test. A subsequent case-control study also revealed a significant association between the haplotype constructed from D18S852 and the 6409T>C polymorphism located in C18orf1 and schizophrenia. In the present study, we screened the C18orf1 gene for mutations and identified a novel single nucleotide polymorphism (SNP), -96T>C in exon 2. This SNP showed significant genotypic (P = 0.048) and allelic association (P = 0.005) with schizophrenia in a case-control study. The distributions of haplotypes defined by D18S852 and -96T>C were different between control and schizophrenia groups (P = 0.021). These findings suggest that C18orf1 or a gene nearby may contribute to the overall genetic risk for schizophrenia.
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PMID:C18orf1 located on chromosome 18p11.2 may confer susceptibility to schizophrenia. 1507 60

Biosynthesis and metabolism of serotonin and catecholamines involve at least eight individual enzymes that are mainly expressed in tissues derived from the neuroectoderm, e.g., the central nervous system (CNS), pineal gland, adrenal medulla, enterochromaffin tissue, sympathetic nerves, and ganglia. Some of the enzymes appear to have additional biological functions and are also expressed in the heart and various other internal organs. The biosynthetic enzymes are tyrosine hydroxylase (TH), tryptophan hydroxylases type 1 and 2 (TPH1, TPH2), aromatic amino acid decarboxylase (AADC), dopamine beta-hydroxylase (DbetaH), and phenylethanolamine N-methyltransferase (PNMT), and the specific catabolic enzymes are monoamine oxidase A (MAO-A) and catechol O-methyltransferase (COMT). For the TH, DDC, DBH, and MAOA genes, many single nucleotide polymorphisms (SNPs) with unknown function, and small but increasing numbers of cases with autosomal recessive mutations have been recognized. For the remaining genes (TPH1, TPH2, PNMT, and COMT) several different genetic markers have been suggested to be associated with regulation of mood, pain perception, and aggression, as well as psychiatric disturbances such as schizophrenia, depression, suicidality, and attention deficit/hyperactivity disorder. The genetic markers may either have a functional role of their own, or be closely linked to other unknown functional variants. In the future, molecular testing may become important for the diagnosis of such conditions. Here we present an overview on mutations and polymorphisms in the group of genes encoding monoamine neurotransmitter metabolizing enzymes. At the same time we propose a unified nomenclature for the nucleic acid aberrations in these genes. New variations or details on mutations will be updated in the Pediatric Neurotransmitter Disorder Data Base (PNDDB) database (www.bioPKU.org).
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PMID:Mutations in human monoamine-related neurotransmitter pathway genes. 1844 57

Two global omics approaches were applied to develop an inventory of differentially expressed proteins and genes in Wig rat, a promising animal model of attention-deficit hyperactivity disorder (ADHD). The frontal cortex, striatum, and midbrain of Wig rat at 4 weeks of age were dissected for proteomics and transcriptomics analyses. Two-dimensional gel electrophoresis detected 13, 1, and 16 differentially expressed silver nitrate-stained spots in the frontal cortex, striatum, and midbrain, respectively. Peptide mass fingerprinting/tandem mass spectrometry identified 19 nonredundant proteins, belonging to 7 functional categories, namely, signal transduction, energy metabolism, cellular transport, protein with binding function, protein synthesis, cytoskeleton, and cell rescue. Interestingly, 10 proteins that were indentified in the present study were also previously reported in studies involving neurodegenerative diseases and psychiatric disorders, such as Alzheimer's disease (AD), Parkinson's disease, and Schizophrenia. Moreover, some of the proteins identified in the midbrain were involved in synaptic vesicular transport, suggesting abnormality in neurotransmitter release in this region. On the other hand, transcriptomics analysis of combined frontal cortex, striatum, and midbrain by rat whole genome 44K DNA oligo microarray revealed highly up-regulated (28) and down-regulated (33) genes. Functional categorization of these genes showed cellular transport, metabolism, protein fate, signal transduction, and transcription as the major categories, with 26% genes of unknown function. Some of the identified genes were related to AD, fragile X syndrome, and ADHD. This is a first comprehensive study providing insight into molecular components in Wig rat brain, and will help to elucidate the roles of identified proteins and genes in Wig rat brain, hopefully leading to uncovering the pathogenesis of ADHD.
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PMID:Proteomics- and transcriptomics-based screening of differentially expressed proteins and genes in brain of Wig rat: a model for attention deficit hyperactivity disorder (ADHD) research. 1845 38

Group II metabotropic glutamate receptors (mGluRs) comprise mGluR2 (mGlu2; encoded by GRM2) and mGluR3 (mGlu3; encoded by GRM3) and modulate glutamate neurotransmission and synaptic plasticity. Here we review the expression and function of mGluR3 and its involvement in schizophrenia. mGluR3 is expressed by glia and neurons in many brain regions and has a predominantly presynaptic distribution, consistent with its role as an inhibitory autoreceptor and heteroceptor. mGluR3 splice variants exist in human brain but are of unknown function. Differentiation of mGluR3 from mGluR2 has been problematic because of the lack of selective ligands and antibodies; the available data suggest particular roles for mGluR3 in long-term depression, in glial function and in neuroprotection. Some but not all studies find genetic association of GRM3 polymorphisms with psychosis, with the risk alleles also being associated with schizophrenia-related endophenotypes such as impaired cognition, cortical activation and glutamate markers. The dimeric form of mGluR3 may be reduced in the brain in schizophrenia. Finally, preclinical findings have made mGluR3 a putative therapeutic target, and now direct evidence for antipsychotic efficacy of a group II mGluR agonist has emerged from a randomised clinical trial in schizophrenia. Together these data implicate mGluR3 in aetiological, pathophysiological and pharmacotherapeutic aspects of the disorder.
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PMID:The group II metabotropic glutamate receptor 3 (mGluR3, mGlu3, GRM3): expression, function and involvement in schizophrenia. 1854 26

Dysbindin (also known as dysbindin-1 or dystrobrevin-binding protein 1) was identified 10 years ago as a ubiquitously expressed protein of unknown function. In the following years, the protein and its encoding gene, DTNBP1, have become the focus of intensive research owing to genetic and histopathological evidence suggesting a potential role in the pathogenesis of schizophrenia. In this review, we discuss published results demonstrating that dysbindin function is required for normal physiology of the mammalian central nervous system. In tissues other than brain and in non-neuronal cell types, the protein has been characterized as a stable component of a multi-subunit complex, named BLOC-1 (biogenesis of lysosome-related organelles complex-1), which has been implicated in intracellular protein trafficking and the biogenesis of specialized organelles of the endosomal-lysosomal system. In the brain, however, dysbindin has been proposed to associate into multiple complexes with alternative binding partners, and to play a surprisingly wide variety of functions including transcriptional regulation, neurite and dendritic spine formation, synaptic vesicle biogenesis and exocytosis, and trafficking of glutamate and dopamine receptors. This puzzling array of molecular and functional properties ascribed to the dysbindin protein from brain underscores the need of further research aimed at ascertaining its biological significance in health and disease.
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PMID:Dysbindin-containing complexes and their proposed functions in brain: from zero to (too) many in a decade. 2150 12


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