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)

The paper deals with a study of 83 patients with different forms of schizophrenia and 15 normals where the methylating activity in converting nicotinamid into methylnicotinamid was determined and the activity of catechol-methyltransferase. In schizophrenic patients there is an increase of the methylating activity which significantly correlated with hallucinatory symptoms in the clinical picture. In patients with cataono-paranoid, paranoid syndromes and simple forms of schizophrenia the methylating activity is seen significantly less frequently. The disappearance of alleviation of hallucinations, due to neuroleptical drugs is accompanied by normalization of the methylating activity. Any significant differences in the excretion of isdarin as an index of cathechol-o-methyltransferase activity in normals and schizophrenic patients was not established.
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PMID:[Several indices of the methylation process in schizophrenic patients]. 1 7

The transmethylation hypothesis of schizophrenia proposes that the disease results from excessive accumulation of methylated derivatives of biogenic amines. To test the hypothesis that an abnormality in S-adenosylmethionine-dependent N-methyltransferase (SAM enzyme) might play a role in schizophrenia, the authors compared SAM enzyme activity of in vitro preparations of 6 brain regions obtained at autopsy from chronic schizophrenics and nonschizophrenic controls. An analysis of variance demonstrated statistically significant differences among brain regions but not between schizophrenics and controls.
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PMID:S-adenosylmethionine-dependent N-methyltransferase activity in autopsied brain parts of chronic schizophrenics and controls. 65 83

Previous studies have focused on the role of the central nucleus of the amygdala (CeA) in cardiovascular and other amygdaloid functions. The combined retrograde tracing/immunohistochemical method was used to test for the presence of enkephalin, neurotensin, neuropeptide Y, and catecholamine neurons within the nucleus of the solitary tract that send efferents to the CeA. After injections of retrograde tracer into the CeA, retrogradely labeled neurons were observed within the caudal, medial nucleus of the solitary tract. Most CeA-projecting neurons were located ipsilaterally within the medial nucleus of the solitary tract at the level of the area postrema. Retrogradely labeled enkephalin- and neurotensin-immunoreactive neurons were found within the medial nucleus of the solitary tract at this level, while retrogradely labeled neuropeptide Y-immunoreactive neurons were found within the medial nucleus of the solitary tract rostral to the area postrema. About 60-74% of CeA-projecting cells were also immunoreactive for tyrosine hydroxylase. Approximately 9% of retrogradely neurons were phenylethanolamine-N-methyltransferase immunoreactive. The results provide evidence that within the nucleus of the solitary tract, peptidergic CeA-projecting neurons have a topographic distribution. In addition, noradrenergic neurons within the A2 group, rather than adrenergic neurons of the C2 group, provide the bulk of catecholaminergic input to the CeA from the nucleus of the solitary tract. Cell counts indicate that each of these peptides may be colocalized (to varying extents) within catecholamine-producing neurons. Also the catecholaminergic and enkephalinergic contribution to the ascending pathway from the nucleus of the solitary tract to the CeA distinguishes it neurochemically from the descending pathway. Thus, although there are afferent and efferent connections between the nucleus of the solitary tract and CeA, their peptidergic/neurotransmitter connections are not necessarily reciprocal. Input from nucleus of the solitary tract peptidergic and catecholaminergic neurons to the CeA may be important in the etiology of a number of pathophysiological conditions including hypertension, gastric ulcers, and schizophrenia.
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PMID:Organization of peptidergic and catecholaminergic efferents from the nucleus of the solitary tract to the rat amygdala. 198 Nov 74

Bipolar affective disorder is a highly heritable condition, as demonstrated in twin, family, and adoption studies. Morbid risk in first degree relatives is four to six times higher than the population prevalence of about 1%. However, the mode of inheritance is complex, and linkage findings have been difficult to replicate. Despite these limitations, consistent linkage findings have emerged on several chromosomes, notably 18p, 18q, 21q, 12q, 4p, and Xq. Two additional areas, 10p and 13q, have shown linkage in regions that appear to overlap with significant linkage findings in schizophrenia. Separate linkage studies in schizophrenia also have targeted the replicated bipolar linkages on 18p and 22q. New methods are being developed for fine mapping and candidate identification. Recent candidate gene studies include some positive results for the serotonin transporter gene on 17q and the catechol-o-methyltransferase gene on 22q. No other candidate gene studies are yet showing replicated results. A convincing demonstration for a susceptibility gene will probably require a mixture of case- control studies, family-based association methods, and pathophysiologic studies.
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PMID:Genetics of bipolar affective disorder. 1112 48

Catechol-o-methyltransferase (COMT) and proline dehydrogenase (PRODH) may both be susceptibility genes for schizophrenia. As part of the evaluation of their roles in psychosis, we used reverse transcription-polymerase chain reaction to measure COMT and PRODH mRNAs in the dorsolateral prefrontal cortex in schizophrenia, bipolar disorder, major depression, and normal controls (n = 15 subjects in each group). We also genotyped two common COMT polymorphisms (-287A/G and 158Val/Met) which might affect its expression. Neither COMT nor PRODH mRNA abundance differed between diagnostic groups, nor when controls were compared with all psychotic patients. COMT mRNA levels were unrelated to COMT genotypes. We conclude that any involvement of COMT and PRODH genes in schizophrenia is not accompanied by significant alterations in their overall mRNA expression, at least in dorsolateral prefrontal cortex. As COMT and PRODH are both located on chromosome 22q11, the results also argue against the hypothesis that schizophrenia is associated with a decrease in expression of all 22q11 genes, as had been suggested by the high prevalence of psychosis in people with hemizygous 22q11 deletions.
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PMID:Catechol-o-methyltransferase (COMT) and proline dehydrogenase (PRODH) mRNAs in the dorsolateral prefrontal cortex in schizophrenia, bipolar disorder, and major depression. 1461 78

A down-regulation of reelin and glutamic acid decarboxylase (GAD) 67 mRNAs was detected in gamma-aminobutyric acid (GABA)ergic cortical interneurons of schizophrenia (SZ) postmortem brains (10), suggesting that the availability of GABA and reelin may be decreased in SZ cortex. In situ hybridization of the mRNA encoding for DNA-methyltransferase 1, which catalyzes the methylation of promoter CpG islands, shows that the expression of this mRNA is increased in cortical GABAergic interneurons but not in pyramidal neurons of SZ brains. Counts of reelin mRNA-positive neurons in Brodmann's area 10 of either nonpsychiatric subjects or SZ patients show that the expression of reelin mRNA is decreased in layer-I, -II, and -IV GABAergic interneurons of SZ patients. These findings are consistent with the hypothesis that the increase of DNA-methyltransferase 1 expression in telencephalic GABAergic interneurons of SZ patients causes a promoter hypermethylation of reelin and GAD(67) and perhaps of other genes expressed in these interneurons. It is difficult to decide whether this dysfunction of GABAergic neurons detected in SZ is responsible for this disease or is a consequence of this disorder. Although at present we cannot differentiate between these two alternatives, it is important to consider that so far a molecular pathology of cortical GABAergic neurons appears to be the most consistent finding associated with SZ morbidity.
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PMID:DNA-methyltransferase 1 mRNA is selectively overexpressed in telencephalic GABAergic interneurons of schizophrenia brains. 1468 36

Inhibitory GABAergic interneurons of prefrontal cortex (PFC) appear to play an important role in the regulation of intermittent pyramidal neuron columnary firing and in the neuronal plasticity that mediate cognitive functions. In schizophrenia (SZ), cognitive defects and dysfunctions in pyramidal neuronal columnary firing appear to depend on abnormalities of GABAergic neurons. These abnormalities include a decrease of GAD67 and reelin expression, which result in a reduction of cortical inhibitory input to spine postsynaptic densities as a result of the decrease of GABA concentration at the synaptic cleft, and of neurotrophic stimuli as a result of the decrease of reelin secreted into the extracellular matrix. Our studies show that alterations in chromatin remodeling related to a selective upregulation of DNA-5-cytosine methyltransferase (DNMT) expression in GABAergic neurons of SZ PFC may induce a hypermethylation of reelin and GAD67 promoter CpG islands, which downregulates their expression. In addition, we report preliminary evidence suggesting that by targeting this chromatin-remodeling deficit with inhibitors of histone deacetylases (HDAC), it may be possible to reduce the DNMT upregulation via a covalent modification of nucleosomal histone tails, underscoring the possibility that by addressing a chromatin remodeling deficit, one may treat psychiatric disorders.
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PMID:GABAergic cortical neuron chromatin as a putative target to treat schizophrenia vulnerability. 1497 67

The enzyme catechol-o-methyltransferase (COMT) transfers a methyl group from adenosylmethionine to catecholamines including the neurotransmitters dopamine, epinephrine and norepinephrine. This methylation results in the degradation of catecholamines. The involvement of the COMT gene in the metabolic pathway of these neurotransmitters has made it an attractive candidate gene for many psychiatric disorders. In this article, we reported our study of association of COMT with schizophrenia in Irish families with a high density of schizophrenia. Three single nucleotide polymorphisms (SNPs) were genotyped for the 274 such families and within-family transmission disequilibrium tests were performed. SNP rs4680, which is the functional Val/Met polymorphism, showed modest association with the disease by the TRANSMIT, FBAT and PDT programs, while the other two SNPs were negative. These SNPs showed lower level of LDs with each other in the Irish subjects than in Ashkenazi Jews. Haplotype analysis indicated that a haplotype, haplotype A-G-A for SNPs rs737865-rs4680-rs165599, was preferentially transmitted to the affected subjects. This was different from the reported G-G-G haplotype found in Ashkenazi Jews, but both haplotypes shared the Val allele. We concluded that COMT gene is associated with schizophrenia and carries a small but significant risk to the susceptibility in the Irish subjects.
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PMID:Variants in the catechol-o-methyltransferase (COMT) gene are associated with schizophrenia in Irish high-density families. 1512 4

Catechol-o-methyltransferase (COMT) plays a major role in dopamine metabolism and has been the object of extensive investigations in subjects affected by schizophrenia. Interest in the enzyme has grown in recent years following positive linkage findings for schizophrenia in the chromosomal region surrounding the COMT gene locus on 22q. In several studies, a gender-specific association of COMT polymorphisms with schizophrenia has been reported and has given rise to speculations on transmission ratio distortions. The present investigation addressed allelic distributions in 307 men and women with respect to the rs165599 A > G polymorphism. No evidence was obtained for gender bias in allelic patterns, nor did we observe association with schizophrenia (p = 0.4). While studies involving same-sex siblings are lacking, gender-specific sharing of alleles does not appear to be a consistent feature of the COMT variant investigated.
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PMID:[No evidence for gender-specific sharing of COMT alleles in schizophrenia]. 1557 May 3

The incidence of aggressive behavior in patients with schizophrenia is higher than in the general population. Among particular gene polymorphisms posited to be involved in psychiatric disorders, the catecholamine-O-methyltransferase (COMT) and serotonin transporter (5-HTTPR) genes have been the focus of recent research on aggression. In this study, we hypothesized that both the COMT and the 5-HTTPR genotypes may be dependent on and related to aggression in Korean patients with schizophrenia. The subjects were 168 unrelated male schizophrenic patients diagnosed according to DSM-IV. Among two psychiatric hospital staff and medical university students, 158 unrelated male subjects with no lifetime history of psychiatric disorders were recruited to establish the COMT and 5-HTTPR genotype distribution in the general population. All episodes of aggression from the last discharge to readmission were rated. The Total Overt Aggression Scale (OAS) score (sum of the scores of all episodes of aggression), highest OAS score (highest individual episode score, 0-16), OAS category, and OAS category score (mean score within each category) were recorded. There were statistically significant effects of COMT genotype on the mean OAS 4 (physical aggression against other people) score and the highest OAS score. The most predictive was the OAS 4 score. There was a statistically significant effect of 5-HTTPR genotype on mean total score. Thus, the COMT gene is associated with the severity of aggression and with physical aggression against other people, whereas the 5-HTTPR gene is associated with the summary score of all episodes of aggression.
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PMID:Association of aggressive behavior in Korean male schizophrenic patients with polymorphisms in the serotonin transporter promoter and catecholamine-O-methyltransferase genes. 1557 82


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