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 previously reported that, from a phenomenological standpoint, the behavioral manifestations of cats chronically intoxicated with amphetamine parallel the evolution of the paranoid psychosis induced by the drug in humans. However, certain manifestations in the cat, such as frozen postures, disjunctive behaviors and postures, cataleptic-like phenomena, obstinate progression, loss of righting reflex and pupillary changes, did not appear to be consistent with the phenomenology of the paranoid psychosis. Since treatment of schizophrenic patients with disulfiram, an inhibitor of norepinephrine synthesis that acts at the level of the enzyme dopamine beta-hydroxylase, thereby leading to increased dopamine concentrations, had been found to profoundly exaggerate psychotic symptomatology, amphetamine behavioral syndrome in the cat as it is modified by pretreatment with disulfiram. Following such pretreatment, a faster development of certain end-stage components of the amphetamine syndrome was obtained. Thus, on the first day, development of a Reactive attitude and of more prominent behavioral disjunction occurred with the combined drug administration as compared with amphetamine alone. In contrast with the facilitation of these behaviors was the absence of dyskinesias and hyperreflexia on that day. Stereotyped behavior, loss of motor initiative and hyperkinetic activity were markedly enhanced and appeared with a shorter latency period on subsequent days of the intoxication cycle. Loss of righting reflex was an early manifestation in these animals. During the later days, the particularly high level of compulsive activity was evident from the occurrence of an obstinate progression syndrome and the performance of stereotyped movements of the head in the presence of a crucifixion posture. In general, modification of the amphetamine effects on behavior was in a direction consistent with comparable features in experimental catatonia and the catatonic form of schizophrenia. The need to integrate such phenomena in any amphetamine model of psychosis is stressed and analogies are drawn with similar features reported in animals treated with bulbocapnine or other psychotogenic compounds and with symptoms of human amphetamine psychosis and schizophrenia.
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PMID:Effects of disulfiram on the amphetamine-induced behavioral syndrome in the cat as a model of psychosis. 124 12

The authors compare schizophrenia with several other diseases and discuss how a few simple models that have already been successfully applied in other cases could be used in the genetic analysis of schizophrenia and MAO activity. Among the diseases discussed are Huntington's disease, xanthomatosis, and diabetes. The authors recommend undertaking multivariate studies of monoamine oxidase, dopamine beta-hydroxylase, and other traits associated with schizophrenia in single, large pedigrees ascertained through schizophrenic probands.
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PMID:Types of disease and models for their genetic analysis. 644 88

Plasma dopamine beta-hydroxylase (DBH) activity was determined in 115 members of a North Swedish geographical isolate with a high frequency of schizophrenia, of which 30 persons had schizophrenia, and was compared with a Middle Swedish population of 185 apparently healthy persons. There was no significant difference between the schizophrenic group and their healthy relatives or between the North and Middle-Swedish populations. The number of persons with very low plasma DBH activity in the North Swedish population appeared to be less than those in the control population.
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PMID:Plasma dopamine beta-hydroxylase activity in a North Swedish isolate with a high frequency of schizophrenia. 729 32

Intron 9 of the human dopamine beta-hydroxylase (DBH) gene was amplified using a long PCR procedure in unrelated patients with schizophrenia and unrelated control subjects. MspI digestion of the PCR fragments showed a two allele polymorphism. A1 and A2 Kruskal-Wallis analysis revealed a significant difference in serum DBH activity among the three groups carrying the A1/A2 genotype, the drug-free and drug treated patients, and the control subjects (H = 12.2, df = 2, p < 0.005), and also a significant difference among the three subgroups of drug-treated patients carrying the genotype of A1/A1, A2/A2 or A1/A2 (H = 10.4, df = 2, p < 0.01). The present results suggest that the MspI polymorphic site in intron 9 of the human DBH gene may be associated with alterations of DBH activity in schizophrenia and with the influence of neuroleptic drugs on the DBH activity as well.
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PMID:A study of the relationship between the DBH activity in serum and a MspI polymorphic site in intron 9 of the human DBH gene in schizophrenia. 890 93

Six allelic fragments were typed by a polymerase chain reaction process with a pair of primers specific for a sequence containing the polymorphic (GT)n repeat, a microsatellite repeat, in the human dopamine beta-hydroxylase (DBH) gene. Their frequencies in unrelated patients with schizophrenia were 0.003 (A1), 0.114 (A2), 0.343 (A3), 0.526 (A4), 0.006 (A5), and 0.009 (A6), and in unrelated control subjects, 0.012 (A1), 0.086 (A2), 0.309 (A3), 0.574 (A4), 0.006 (A5), and 0.012 (A6). Kruskal-Wallis analysis revealed significant differences among the three groups, the drug-free and drug-treated patients, and the control subjects, in serum DBH activity of the subjects whose genotype was A2/A3 (H = 6.0, p < .05) or A3/A3 (H = 9.8, p < .01), in serum homovanillic acid concentration of those whose genotype was A3/A4 (H = 7.7, p < .025), and in serum tyrosine concentration of those whose genotype was A4/A4 (H = 8.3, p < .02). Mann-Whitney U test showed that in the subjects carrying the A3/A4 genotype, serum noradrenaline concentration of drug-treated patients was significantly higher than that of control subjects (N = 58, p < .02). These results suggest that genotypic polymorphism of the human DBH is likely to be associated with biochemical variability of the catecholamine pathway in schizophrenia.
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PMID:Is the polymorphic microsatellite repeat of the dopamine beta-hydroxylase gene associated with biochemical variability of the catecholamine pathway in schizophrenia? 908 94

Two parts of the dopamine beta-hydroxylase (DBH) gene, one a 7.5-kb single copy fragment (F1) spanning the 5'-flanking region to exon 3 and the second a 9.0-kb single copy fragment (F2) spanning exon 3 to exon 7, were amplified by a long PCR procedure in 161 unrelated patients with schizophrenia and 67 unrelated control subjects. The PCR products were completely digested with the restriction enzyme TaqI. These subjects were classified into genetic subgroups according to the TaqI restriction fragment length polymorphisms (RFLPs) for the human DBH gene, and the association of the TaqI RFLPs with biochemical alterations of the catecholamine pathway in schizophrenia was then examined. The frequencies of the two TaqI polymorphic sites did not show significant differences between the patients and control subjects, but the TaqI RFLPs were found to be associated with biochemical alterations of the catecholamine pathway in schizophrenia.
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PMID:TaqI polymorphic sites at the human dopamine beta-hydroxylase gene possibly associated with biochemical alterations of the catecholamine pathway in schizophrenia. 956 83

The presence of a polymorphic (GT)(n) repeat, a microsatellite repeat, at the human dopamine beta-hydroxylase (DBH) gene had been previously investigated in healthy people and in schizophrenic patients. The different DBH genotypes had been found to be associated to different DBH biochemical function, but no differences were found in the allelic and genotype frequencies between schizophrenic and control groups. To further clarify the potential involvement of the variation at the DBH gene in schizophrenia we have studied the DBH (GT)(n) repeat in a sample of 47 Spanish schizophrenic patients, in their healthy relatives (n = 72), and in a control population (n = 74). We have been able to identify five different variants of the DBH gene (A1, A2, A3, A4, A5) in the different groups. Subsequent statistical analysis revealed that the genotypes as well as the allele frequencies did not differ significantly among schizophrenic patients and the control population. Interestingly, the allelic variant A2 and the genotype A4/A2 were significantly more frequent in schizophrenic patients as compared with their healthy relatives. However, the association of the A2 allele with schizophrenia was not supported by the haplotype relative risk analysis of transmitted versus nontransmitted alleles. Therefore, although it will be important to extend the present analysis in a larger sample of schizophrenic patients and controls, our results suggest that the (GT)(n) does not seem to play a major role in the genetics of schizophrenia at least in this group of Spanish schizophrenic patients. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:88-92, 2000.
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PMID:Analysis of the polymorphic (GT)(n) repeat at the dopamine beta-hydroxylase gene in Spanish patients affected by schizophrenia. 1068 59

The cerebellum seems to play a critical role in many motor and cognitive functions, including those that are disturbed in schizophrenia. Although dopamine is known to influence the motor or cognitive functions mediated by other brain regions and to play a role in the pathophysiology of schizophrenia, the cerebellum has not been thought to be a target of dopamine-containing axons. However, given recent reports of dopamine receptors in the cerebellum, we sought to determine whether axons immunoreactive for the proteins involved in dopamine synthesis and reuptake are present in the cerebellum of macaque monkeys. We found that axons immunoreactive for the dopamine membrane transporter, a specific marker of dopamine axons, were present in high density, but only in certain lobules of the cerebellar vermis. In addition, these axons were found principally in the granule cell layer, where they densely arborized immediately subjacent to the Purkinje cells. Similarly, axons labeled for tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, were also present in high density in the granule cell layer of the same lobules of the vermis. In contrast, axons immunoreactive for dopamine beta-hydroxylase, a marker of noradrenergic axons, exhibited a different and more widespread pattern of innervation. These findings are consistent with a dopamine innervation of the primate cerebellum that is both lobular- and laminar-specific, and they suggest that dopamine may play a role in certain cerebellar functions.
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PMID:Tyrosine hydroxylase- and dopamine transporter-immunoreactive axons in the primate cerebellum. Evidence for a lobular- and laminar-specific dopamine innervation. 1073 21

In neurons, pituitary adenyl cyclase activating peptide (PACAP) stimulates signaling cascades, involving cAMP and calcium. PACAP appears to play a role in up-regulation of tyrosine hydroxylase and dopamine beta-hydroxylase via protein kinase C and/or protein kinase A. Furthermore, the PACAP gene (ADCYAP1) is located in chromosome 18p11, where linkage of bipolar disorders and schizophrenia has been reported. In this study, we scanned the coding region of the PACAP gene for mutations in 24 Japanese patients with schizophrenia and 24 Japanese patients with bipolar disorders. No variant in the coding region was found. One polymorphism, INV3-37A/T, in the third intron was detected. Case-control comparisons revealed no significant association between this polymorphism and schizophrenia or bipolar disorders. This study did not provide evidence for the contribution of the PACAP gene to the etiology of schizophrenia or bipolar disorders in the Japanese population.
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PMID:Association analysis of the pituitary adenyl cyclase activating peptide gene (PACAP) on chromosome 18p11 with schizophrenia and bipolar disorders. 1151 50

Increasing evidence during the last few years suggests that there are gender-specific differences in schizophrenia, influencing the age of onset, treatment outcome and the prevalence of negative symptoms. With respect to the latter in postmortem brain and cerebrospinal fluid of schizophrenic patients with negative symptoms a reduction of dopaminergic activity became evident. Measures of noradrenergic activity, dopamine beta-hydroxylase and the metabolite MHPG, appear to decrease with brain atrophy seen in patients with negative symptoms. Serotonergic activity tends to be low in patients with impaired cognitive function as is seen in negative schizophrenia. In these patients ventricular enlargement is associated with the severity of negative symptoms, low monoamine activity and low cerebral glucose metabolism. On the other hand atypical antipsychotic drugs that modulate also glutamate receptor activity, suggest an additional alternative mechanism of antipsychotic action beyond aminergic neurotransmitters. These drugs improve glutamatergic transmission and decrease negative symptoms; this suggests a glutamatergic deficiency as an extension of the dopamine model. The glutamate-dopamine interaction illustrates the importance of cross-talk between projections to the cortex, striatum, and lower brainstem for the expression of negative symptomatology. On the other hand, estradiol-17beta the most potent female sex hormone influences not only primary and secondary sexual characteristics but also embryonal and fetal growth as well as development of the brain aminergic networks, which are involved in schizophrenia. Estradiol-l7beta possesses neuroprotective properties, which are relevant for the course of schizophrenia and this may explain the pronounced gender differences with respect to progression and therapeutic response of schizophrenia. The present review attempts an update and synthesis of the information about the hormonal influence on neuronal pathways in negative symptoms of schizophrenia. It shows that estradiol-l7beta influences transporters and receptors as well as the morphological appearance of neuronal systems and that it may be an integral part of the neuroprotective system ameliorating schizophrenia.
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PMID:Effects of estrogen on brain development and neuroprotection--implications for negative symptoms in schizophrenia. 1265 Jun 83


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