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)

Striatopallidal output neurons, which coexpress D2-dopamine receptors and NMDA receptors, are logically a potential site of interaction between corticostriatal glutamatergic input and dopaminergic systems. Recent hypotheses about the etiology of schizophrenia have implicated both excitatory amino acid and dopamine systems. The present study was designed to examine, in vivo, the interaction between D2-dopamine receptors and NMDA receptors in the regulation of the expression of the early immediate genes (IEGs), zif 268 and jun B, in striatopallidal neurons. We tested whether coadministration of NMDA antagonists interacted with the actions of the D2 agonist, quinpirole, on IEG expression following dopamine depletion with reserpine. When rats were pretreated with the non-competitive NMDA receptor antagonists, MK 801 (1 mg/kg) or PCP (20 mg/kg), together with quinpirole, the quinpirole reversal of reserpine induction of zif 268 mRNA was potentiated in all regions examined. MK 801 alone had no significant effect on reserpine induction of zif 268 mRNA. Pretreatment with the competitive NMDA receptor antagonist, CPP (5 mg/kg), did not significantly alter the dose response of zif 268 mRNA expression to quinpirole in any region. There was no significant effect of MK 801 on jun B mRNA expression, either on the response to quinpirole or when administered alone with reserpine. Our findings provide evidence of an interaction between the NMDA receptor channel system and the D2-dopamine system on a molecular level in striatopallidal neurons carrying output from the basal ganglia.
Brain Res Mol Brain Res 1998 Aug 15
PMID:Potentiation of D2-dopamine receptor-mediated suppression of zif 268 by non-competitive NMDA receptor antagonists in reserpinized rats. 972 66

Our previous findings in female rats suggest that the potent effects of sex steroids on mood and mental state may be mediated, in part, by the effect of estrogen on the 5-hydroxytryptamine2A receptor (5-HT2AR) in brain. The aim of the present study was to determine the effect of acute (approximately 32h) sex steroid manipulation on central 5-HT2AR in the adult male Wistar rat. Castration (under halothane anesthesia) decreased while testosterone or estrogen, but not 5alpha-dihydrotestosterone (5alpha-DHT), increased significantly the 5-HT2AR mRNA content in dorsal raphe nucleus and the density of 5-HT2AR binding sites in frontal, cingulate and primary olfactory cortex and nucleus accumbens. The lack of effect of 5alpha-DHT, a potent androgen which cannot be converted to estrogen, suggests that the action of testosterone depends upon its conversion to estrogen by aromatase. This may also explain why estrogen, but not testosterone or 5alpha-DHT, increased the density of 5-HT2AR binding sites in the caudate-putamen, a brain region where aromatase is scarce. These findings are discussed in relation to the possible role of the 5-HT2AR in depression, schizophrenia and Alzheimer's Disease.
Brain Res Mol Brain Res 1998 Aug 31
PMID:Testosterone as well as estrogen increases serotonin2A receptor mRNA and binding site densities in the male rat brain. 972 88

A common missense mutation of the methylenetetrahydrofolate reductase (MTHFR) gene (C677T) has been shown to be a risk factor for premature cardiovascular disease and neural tube defect. Deficient activity of MTHFR has also been implicated in the pathogenesis of psychiatric conditions such as schizophrenia and affective disorders. Arinami et al found an increased frequency of homozygosity for the mutated type (T677) of the MTHFR gene in schizophrenia and depression. We tried to replicate this finding in a sample of 343 patients with schizophrenia, 143 with bipolar disorder, 71 with unipolar depression, and 258 controls; however, there was no significantly increased frequency of homozygosity for the T677 allele in any of the diagnostic groups, compared to the controls. Our results suggest that homozygosity for the T677 allele of the MTHFR gene is unlikely to play a major role in the pathogenesis of schizophrenia or affective disorders in our sample.
Mol Psychiatry 1998 Sep
PMID:C677T polymorphism in methylenetetrahydrofolate reductase gene and psychoses. 1020 43

During the past decade numerous studies have been published describing chromosomal regions potentially linked with schizophrenia. Unfortunately, none of these studies has been able to conclusively identify any specific gene that predisposes to schizophrenia. Typically evidence for linkage is seen on large chromosomal regions, as expected, containing tens or even hundreds of genes. Furthermore, attempts to replicate the findings have rarely been successful leaving a confusion about the existence of predisposing genes for schizophrenia in a particular region of the genome. We have carried out linkage analysis in a set of 62 pedigrees rising from a genetically isolated population of Finland with markers on six chromosomal regions earlier suggested to harbor predisposing genes for schizophrenia, namely 3p, 5q, 6p, 8p, 20p, and 22q. We were not able to find significant evidence for linkage on any of these chromosomal regions. However, some support for linkage was found on all studied chromosomal regions, except 3p.
Mol Psychiatry 1998 Sep
PMID:Linkage analysis of putative schizophrenia gene candidate regions on chromosomes 3p, 5q, 6p, 8p, 20p and 22q in a population-based sampled Finnish family set. 977 82

A large multiplex schizophrenia pedigree ascertained from the Micronesian nation of Palau was genotyped with 406 microsatellite DNA markers evenly distributed throughout the genome. Assuming autosomal dominant inheritance, the highest genome-wide lod scores were found for DNA loci mapping to 2p13-14; the maximum lod score was 2.17 (theta = 0.05) at D2S441. A nonparametric APM analysis was also suggestive at D2S441 (APM score = 2.96, P = 0.011). Of the 14 affected cases in this extended family, eight share a large haplotype in this region spanning approximately 11 cM. When 16 other families containing 65 schizophrenic cases were typed in a follow-up study of this region, the maximum lod score remained positive (maximum at D2S441 1.69, theta = 0.20). APM results also remained positive at D2S441 for all 17 families (APM score = 4.87, P = 0.0006). The linkage and haplotype sharing results provide suggestive evidence for a 2p locus predisposing to schizophrenia in a subset of families in the Palauan population.
Mol Psychiatry 1998 Nov
PMID:Evidence for a chromosome 2p13-14 schizophrenia susceptibility locus in families from Palau, Micronesia. 985 78

Mutations in ion channels have been found to cause a variety of mendelian genetic diseases, and polyglutamine repeat expansion is a newly recognized pathogenic mechanism that causes several rare, genetic, late-onset neurological syndromes. Polymorphic polyglutamine tracts are present in a recently described human, calcium-activated potassium channel, KCNN3 (also known as hKCa3), and alleles of this gene that contain longer repeats have been associated with schizophrenia. The physiological function of the channel is consistent with an etiological role in this disease; drugs designed to target this channel might therefore provide novel psychotherapeutics.
Mol Med Today 1998 Dec
PMID:A piece in the puzzle: an ion channel candidate gene for schizophrenia. 986 21

Neuronal nicotinic receptors (nAChRs) have been implicated in pathology associated with neurological diseases and aberrant cognitive states such as addiction and schizophrenia. The design of subtype-specific cholinergic drugs is dependent on identification of key amino acids that play a significant role in determining subunit-specific agonist efficacy. 1,1-Dimethyl-4-phenylpiperazinium (DMPP) and a series of piperazium (PIP)-derived cholinergic agonists (1,1 dimethyl-4-acetylpiperizinium iodide, EthylPIP, PropylPIP, and ButylPIP) were used to identify a site (position 84) in homomeric neuronal nAChRs, which is a partial determinant of pharmacological specificity. In contrast to absolutely conserved amino acids within the nicotinic superfamily, the amino acid in position 84 can be polar or nonpolar. The addition of one methylene to PropylPIP to form ButylPIP eliminated channel activation of but not binding to the chick alpha7 homomeric nAChR (leucine in position 84). In rat alpha7 (glutamine in position 84), ButylPIP was an agonist. 1, 1-Dimethyl-4-phenylpiperazinium, a structural analog of ButylPIP, activates the rat alpha7 but is a weak partial agonist of the chick alpha7. Mutation of the chick alpha7 (L84Q) restored activation by ButylPIP, and the corresponding mutation in rat alpha7 (Q84L) abolished activation by ButylPIP. These mutations had moderate effects on the apparent affinity for acetylcholine, increasing its affinity for chick alpha7 and decreasing it for rat alpha7. Thus, the amino acid in position 84 (a residue on the periphery of the highly conserved loop A of the cys-loop superfamily of receptors) can potentially be exploited to produce subtype-specific drugs and can provide insights into the structure of the binding domain.
Mol Pharmacol 1999 Jan
PMID:Identification of a new amino acid residue capable of modulating agonist efficacy at the homomeric nicotinic acetylcholine receptor, alpha7. 988 91

Borna disease virus (BDV), a negative-strand RNA virus, has been reported to be associated with severe psychiatric disorders. The association is mainly based on the findings that patients with schizophrenia and depression have a higher seroprevalence rate of BDV-specific antibodies than controls. In addition, psychiatric patients were also found to have a higher detection rate of BDV transcripts in their blood than controls. By using an improved Western blot analysis, we first demonstrated that Chinese schizophrenic patients from Taiwan also have a higher seroprevalence of BDV-specific antibodies than controls (12.1% vs 2.9%, P< 0.001), providing support to the positive association between BDV and psychiatric disorders in our population. Because of the contagious nature of viral infection, we further examined patients' family members and mental health workers, who have close contact with patients. We found that both groups also have a higher seroprevalence of BDV-specific antibodies, 12.1% and 9.8%, respectively, than controls. This finding provides some evidence for a possible human-to-human transmission of Borna disease virus. Our finding needs further independent verification from other research groups and the clinical relevance of this preliminary observation deserves further study.
Mol Psychiatry 1999 Jan
PMID:High seroprevalence of Borna virus infection in schizophrenic patients, family members and mental health workers in Taiwan. 1008 6

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.
Mol Psychiatry 1999 Jan
PMID:Alterations in synaptic proteins and their encoding mRNAs in prefrontal cortex in schizophrenia: a possible neurochemical basis for 'hypofrontality'. 1008 7

L1 and Thy-1 are members of the immunoglobulin (Ig) superfamily of cell adhesion molecules (CAMs) that are vital for normal neural development. Abnormalities in CAM expression could lead to the histological abnormalities that have previously been described in the frontal cortex of patients with schizophrenia. A postmortem immunohistochemical study of L1 and Thy-1 in the normal human prefrontal cortex revealed positive immunostaining of axons in all layers of the cortex. Quantifying the intensity of immunostaining in the prefrontal cortex of patients with schizophrenia, bipolar disorder and depression failed to reveal any significant differences when compared to that of normal controls.
Mol Psychiatry 1999 Jan
PMID:Immunohistochemical localization of the cell adhesion molecules Thy-1 and L1 in the human prefrontal cortex patients with schizophrenia, bipolar disorder, and depression. 1008 8


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