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)

1. PE is present in the brain in tiny quantities; it is heterogeneously distributed and present in synaptosomes. 2. It is synthesised from phenylalanine by L-AADC and oxidatively deaminated by MAO-B. Its turnover is remarkably fast. 3. Its concentration, particularly in the caudate nucleus, is affected by MAO inhibition (increased), lesion of the Substantia nigra (decreased), amine depletion (increased) and antipsychotic drugs (increased). 4. When iontophoresed (or injected) it amplifies the effects of DA and NA (and their agonists) but is without effect on other neurotransmitters. 5. It is suggested that it acts postsynaptically as a neuromodulator of catecholaminergic neurotransmission and that it is involved in the mechanism of action of Deprenyl; it is also suggested that it, or its principal metabolite PAA, may be involved in the aetiology of schizophrenia, depression and aggression as well as perhaps in other neuropsychiatric conditions.
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PMID:Phenylethylaminergic modulation of catecholaminergic neurotransmission. 165 28

The positive-negative distinction of schizophrenia has emerged as a valid means of clarifying its heterogeneity. Despite evidence that the two symptom classes may reflect different dimensions of the disease, there is presently no integrated model for understanding of the pathophysiology of these symptoms and their co-occurrence in schizophrenia. We propose that negative phenomena of schizophrenia may be a variant of Parkinsonism. This view is supported by the overlap with Parkinsonism in terms of clinical features, neurochemistry, pharmacology, as well as neuroradiological and neuropathological aspects. As such, negative symptoms may be a manifestation of disease of the basal ganglia and constitute the core pathology in schizophrenia. Positive symptoms, conversely, may reflect an "accessory" process related to a compensatory increase in striatal and limbic dopamine activity following an injury to the dopaminergic system. In the present communication we present a series of studies that support the association of negative schizophrenia and Parkinsonism. Based on this evidence, we suggest that schizophrenic patients with prominent negative symptoms might be managed like patients with Parkinson's disease, namely, with dopaminergic drugs and MAO-B inhibitors. Finally, the association of negative schizophrenia with Parkinsonism raises the possibility that adrenal medullary tissue transplantation, which may benefit a selected group of Parkinsonian patients, may be a future promising therapy for refractory negative schizophrenia.
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PMID:The relationship of negative schizophrenia to parkinsonism. 214 20

The activities of the A and B forms of the enzyme monoamine oxidase (MAO, E.C. 1.4.3.4) have been assessed with the substrates 5-hydroxytryptamine and benzylamine respectively in seven areas of the brains of 39 patients with schizophrenia and 44 control subjects. Whereas previous studies have found the enzyme unchanged in brain in schizophrenia, in this study there was a modest but significant decrease in the activity of MAO-B in frontal and temporal cortices and in amygdala. This decrease could not be accounted for by neuroleptic medication, age, sex or post-mortem variables. In a series of 22 patients who had been assessed in life, the reduction in MAO-B activity was found to be associated specifically with the presence of negative symptoms (flattening of affect and paucity of speech). The findings are therefore consistent with other evidence for structural and neurochemical change in the temporal lobe that have been associated with the type II (defect state) syndrome of schizophrenia. The change in enzyme activity is unlikely to be related to a change in monoamine metabolism but may reflect a disturbance in glial function. The change in MAO-B activity in brain in this study is confined to particular areas of brain and a subgroup of patients; it is thought to be entirely unrelated to earlier reports of reductions of enzyme activity in platelets, which are probably attributable to prolonged neuroleptic medication.
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PMID:Selective decreases in MAO-B activity in post-mortem brains from schizophrenic patients with type II syndrome. 344 67

Mitochondrial monoamine oxidase (MAO), type B, has been implicated in the etiology of schizophrenia. We have found the phospholipid, phosphatidylserine (PS) to be a highly specific inhibitor of MAO-B, which has led us to postulate that the PS-MAO interaction might offer a basis for the lower MAO levels observed in platelets from certain schizophrenic populations. In this study we compared platelet MAO activity with phospholipid composition in a group of normals and chronic paranoid schizophrenics. The phospholipids in platelets and erythrocytes were extracted and separated by high-performance liquid chromatography into major classes phosphatidylcholine (PC), phosphatidylethanolamine, lysophosphatidylethanolamine, phosphatidylinositol and PS. The paranoid subjects showed statistically significantly lower MAO activity as well as higher mean levels of PS and lower levels of PC in both platelets and erythrocytes, consistent with our hypothesis. The Ca2+-stimulated synthesis of serine-lipid in platelets was also monitored by incorporation of radioisotope into lipid extracts from 14C-labelled serine substrate, and no significant differences were found between subjects groups with respect to this parameter.
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PMID:A comparison of platelet monoamine oxidase activity and phosphatidylserine content between chronic paranoid schizophrenics and normal controls. 374 56

Fibroblasts have emerged as one of the best systems in which to study several genetically inherited diseases. Their use avoids the contaminating effects of medication and other environmental factors. Moreover, fibroblast cells cultured in vitro can express several biochemical parameters which are characteristic of neuronal cells. We have studied fibroblast MAO-A and glucose oxidation and platelet MAO-B from schizophrenic patients and control subjects. Fibroblasts from schizophrenics showed an increased glucose oxidation in two different experiments conducted (122% and 126% compared to controls). No changes were found in the levels of fibroblast MAO-A or platelet MAO-B activity. Possibly these alterations in glucose oxidation may be associated with a generalized membrane abnormality which has been reported in schizophrenia.
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PMID:Glucose oxidation and monoamine oxidase activity from the fibroblasts of schizophrenic patients and controls. 772 92

Monoamine oxidases (MAO) A and B, which are encoded by two distinct genes located on the human X chromosome, are both involved in the oxidative metabolism of dopamine. Decreased levels of platelet MAO-B activity has been reported in patients with schizophrenia and genetic variation in MAO activity had been proposed as a significant factor in the etiology of this disease. We carried out an association study using two intragenic polymorphisms within the MAO-A and MAO-B genes in 110 schizophrenic patients and 87 control subjects. For each polymorphic marker, no significant difference in allelic frequencies was observed between patients and controls. Nevertheless, a trend toward an association between allele 1 of the MAO-B gene and paranoid schizophrenia was found. Our results do not support the hypothesis that inherited variants of MAO genes might play a major role in a genetic predisposition to schizophrenia. Since several previous reports found a low MAO-B platelet activity in patients with paranoid schizophrenia, the identification of polymorphisms related to enzyme activity would be useful.
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PMID:Association study between schizophrenia and monoamine oxidase A and B DNA polymorphisms. 880 32

The monoamine oxidase B (MAO-B) gene was examined in 100 alleles derived from 80 Caucasian, 10 African-American, 5 Asian, and 5 Native American male patients with schizophrenia to identify sequence changes that might be associated with the disease. Approximately 235 kb of genomic sequence, primarily in coding regions, were screened by dideoxy fingerprinting, a modification of single-strand conformational polymorphism (SSCP) analysis that detects virtually 100% of sequence changes [Sarkar et al. (1992): Genomics 13:441-443; Liu and Sommer (1994): PCR Methods Appl 4:97-108]. No sequence changes of likely functional significance were identified, suggesting that mutations affecting the structure of the MAO-B protein are uncommon in the general population and are unlikely to contribute significantly to the genetic predisposition to schizophrenia. Eight polymorphisms were identified in African-Americans and Native Americans, but none were identified among Caucasians. Of the eight observed polymorphisms, a set of five transitions and one microdeletion was identified within approximately 17 kb of genomic sequence in the same 3 African-American individuals, while the remaining 7 African-Americans had a sequence identical to that in Caucasians. The presence of two such haplotypes, without intermediates, is compatible with the hypothesis that germline mutations can occur in clusters, as also suggested by other recent findings.
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PMID:Screening the monoamine oxidase B gene in 100 male patients with schizophrenia: a cluster of polymorphisms in African-Americans but lack of functionally significant sequence changes. 903 5

In order to study the putative monoamine oxidase (MAO) inhibitory side effect of neuroleptics and simultaneous changes in platelet serotonin content both MAO-B activity and serotonin (5-HT) content in platelets of 30 healthy volunteers and 50 schizophrenic patients treated with neuroleptics were investigated. Our results have shown significantly lower MAO-B activity (15.26 +/- 6.81 S.D. vs. 8.63 +/- 3.82 mmol/hour/10(9) platelets) and higher platelet 5-HT content (906.19 +/- 285.33 vs. 1,727.85 +/- 947.40 ng/10(9) platelets) in the schizophrenic group. Platelet MAO-B activity was considerably lower in paranoid and residual schizophrenics compared with other patients, however, no difference was found in platelet 5-HT content between different subtypes of schizophrenia. Various neuroleptic treatments did not produce different effects either on platelet serotonin content or platelet MAO-B activity.
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PMID:MAO inhibitory side effects of neuroleptics and platelet serotonin content in schizophrenic patients. 956 10

Two X-linked microsatellites, (AC) n repeats at the monoamine oxidase (MAO)-A locus and (TG)n repeats at the MAO-B locus, were studied in 140 unrelated Caucasian male patients with schizophrenia and 91 unrelated Caucasian male controls. Among these subjects, we totally typed out nine alleles for the (AC) n repeats and eight alleles for the (TG) n repeats by using a PCR-based procedure. Allelic frequencies of either (AC) n repeats or (TG) n repeats were not found to be significantly different between patients and controls. However, a significant excess of the (AC)18/(TG)23 haplotype with a relative risk of 4.05 (95%; CI 1.15-14.26) was observed in patients with schizophrenia (Fisher's P = 0.011). The coefficient of linkage disequilibrium (delta) for the (AC)18/(TG)23 haplotype was 0.019 in schizophrenic patients and -0.046 in control subjects, respectively. The latter reached statistical significance (chi 2 = 6.02; df = 1; P < 0.02). The present findings suggest that linkage disequilibrium between polymorphic loci for human MAO-A and MAO-B may be associated with schizophrenia, and the (AC)18/(TG)23 haplotype may render an individual more vulnerable to such an illness.
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PMID:A study of linkage disequilibrium between polymorphic loci for monamine oxidases A and B in schizophrenia. 1069 23

In the course of investigating the mechanisms underlying the beneficial effect of fluvoxamine augmentation on negative symptoms of schizophrenia, the authors found a reduction in human platelet monoamine oxidase-B activity after 5 weeks of treatment. This unexpected finding raised the possibility that MAO activity may be one of the factors altered by chronic tricyclic or SSRI antidepressant treatment. The current study examined the effect of long-term administration, up to 6 weeks, of fluvoxamine, desipramine or saline on MAO-A and MAO-B activities in rat striatum, frontal cortex and liver. No differences were noted between drug-treated groups and their saline-treated controls. The hypothesis that long-term treatment with tricyclic and SSRI antidepressants alters MAO activity was not supported. MAO is not among proteins whose activity may be altered by chronic tricyclic or SSRI antidepressant treatment.
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PMID:MAO-A and MAO-B activities in rat striatum, frontal cortex and liver are unaltered after long-term treatment with fluvoxamine and desipramine. 1070 94


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