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 increased aggressive behavior in schizophrenic patients may be associated with a polymorphism at codon 158 of the catechol O-methyltransferase (COMT) gene that encodes a low enzyme activity variant. The finding has been replicated by one group, but not others. The discordant findings could be due to statistical errors or methodological issues in the assessment of aggressive/violent behavior. Consequently, additional studies are needed. Patients with schizophrenia (SZ) were assessed for violent behavior using the Lifetime History of Aggression (LHA) scale, an 11-item questionnaire that includes Aggression, Self-Directed Aggression, and Consequences/Antisocial Behavior subscales. DNA was genotyped for the COMT 158 polymorphism, as well as a functional polymorphism in the monoamine oxidase A (MAOA) gene promoter. Similar to our previously reported findings, a statistically significant association was found between aggressive behavior in SZ and the COMT 158 polymorphism; mean LHA scores were higher in subjects homozygous for 158Met, the low enzyme activity COMT variant (F(2,105) = 5.616, P = 0.005). Analysis of the major LHA subscales revealed that the association with 158Met was due to high scores on the Aggression, and Self-Directed Aggression subscales, but not the Consequences/Antisocial Behavior subscale. No significant association was detected for the MAOA gene alone. Our findings provide further support that COMT is a modifying gene that plays a role in determining interindividual variability in the proclivity for outward and self-directed aggressive behavior found in some schizophrenic patients.
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PMID:Aggressive behavior in schizophrenia is associated with the low enzyme activity COMT polymorphism: a replication study. 1281 35

Biogenic amine synthesis and degradation are involved in the pathogenesis of schizophrenia. Catechol-O-methyltransferase and monoamine oxidase enzymes are important agents in the metabolic inactivation of these neurotransmitters (ie, dopamine, serotonin, and norepinephrine). Functional polymorphism in the catechol-O-methyltransferase and monoamine oxidase A genes causes variation in enzyme activities. We investigated the relationship of catechol-O-methyltransferase Val158Met and monoamine oxidase A promoter repeat polymorphism with response to conventional neuroleptic treatment in schizophrenia.Ninety-four schizophrenic patients formed 2 different study populations. The responders had experienced a fair and steady response to conventional neuroleptics. The nonresponders had failed to achieve an acceptable response to conventional neuroleptics. We also used a control population of 94 age-matched and gender-matched blood donors. Genotyping of the catechol-O-methyltransferase and monoamine oxidase A genes was performed by polymerase chain reaction.Forty-three percent of the nonresponders had a low activity catechol-O-methyltransferase genotype compared with 16% of the responders (P = 0.009). Monoamine oxidase A genotype alone did not differ significantly between the groups. Moreover, the risk of having both low-activity catechol-O-methyltransferase and monoamine oxidase A genotypes was over 6 times more common (odds ratio = 6.16, P = 0.03) in the nonresponders compared with responders. The whole population of patients with schizophrenia did not differ from the controls.The low-activity catechol-O-methyltransferase genotype may be associated with unsatisfactory drug response to conventional neuroleptics or alternatively be involved in a subset of schizophrenics. The role of monoamine oxidase A genotype seems to be additive in this respect.
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PMID:Catechol-O-methyltransferase and monoamine oxidase A genotypes and drug response to conventional neuroleptics in schizophrenia. 1452 Jan 17

Several lines of evidence suggest that tardive dyskinesia (TD) may be associated with altered dopaminergic neurotransmission. We hypothesized that deranged dopamine degradation enzyme activities might be related to the susceptibility to TD through altered dopaminergic neurotransmission in the central nervous system. In the present study, we investigated the relationship between the gene polymorphisms of three dopamine degradation enzymes and TD. We genotyped the valine/methionine polymorphism of codon 108/158 in the catechol-O-methyltransferase (COMT) gene, the 30-bp repeat polymorphism in the promoter of the monoamine oxidase A (MAOA) gene, and the A/G polymorphism in intron 13 of the monoamine oxidase B (MAOB) gene in 206 Japanese patients with schizophrenia. No significant difference was found in total scores on the Abnormal Involuntary Movement Scale (AIMS) among the subject groups, sorted according to the COMT, MAOA and MAOB genotypes. Moreover, no significant difference was found in allele frequencies between patients with TD and patients without TD for any of the polymorphisms. As both COMT and MAO genes are involved in degrading catecholamines, we also sought evidence for additive and epistatic effects, but none was observed. Our data, therefore, do not support the hypothesis that polymorphisms in COMT, MAOA, and MAOB genes are involved individually or in combination in the predisposition to TD.
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PMID:Polymorphisms of dopamine degradation enzyme (COMT and MAO) genes and tardive dyskinesia in patients with schizophrenia. 1526 99

A large body of evidence suggests that suicidal behavior is associated with altered noradrenergic neurotransmission. Norepinephrine is degraded by monoamine oxidase A (MAOA) and catechol-O-methyl transferase (COMT). Our hypothesis is that the genes encoding MAOA and COMT might contain genetic variants conferring increased risk for suicidal behavior in schizophrenia and that both genes may interact each other. In order to test this hypothesis, we genotyped the promoter VNTR polymorphism in the MAOA gene and three COMT polymorphisms: -287A>G, Val/Met and 3'UTR C Ins/Del in a cohort of 270 schizophrenics in which 92 attempted suicide. No association between suicide attempt and the MAOA VNTR (P = 0.382), Val108/158Met (P = 0.788) or -287A>G (P = 0.420) polymorphisms was found, however, a slight significant finding was found for 3'UTR polymorphism (P = 0.050). Haplotype analysis for COMT gene revealed no association between suicide attempts and haplotype distribution (P = 0.451). As we tested for epistasis between MAOA VNTR and COMT Val/Met, we found no significant interaction in conferring risk for suicide attempts (P = 0.545). These results suggest that epistasis between MAOA and COMT genes may not influence suicidal behavior in patients with schizophrenia.
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PMID:Gene-gene interaction between MAOA and COMT in suicidal behavior: analysis in schizophrenia. 1672 19

Genes involved in dopamine neurotransmission are interesting candidates to be analyzed in schizophrenia and aggressive behavior. Therefore, we analyzed the functional polymorphisms of the dopamine receptor D4 (DRD4) and monoamine oxidase A (MAO-A) genes in a sample of 71 schizophrenic patients assessed with the Overt Aggression Scale to measure aggressive behavior. CLUMP analysis of the DRD4 48-bp repeat-exon III polymorphism in schizophrenic patients showed significant differences between the aggressive behavior and the nonaggressive groups (T1 = 18.77, d.f. = 6, p = 0.0046; T3 = 6.54, p = 0.0195). However, analysis of the promoter polymorphism of the MAO-A gene revealed no significant association between aggressive and nonaggressive patients. Finally, analysis of Overt Aggression Scale dimensions exhibited significant differences for the DRD4 and MAO-A genes. Our preliminary findings suggest that the DRD4 and MAO-A genes may be involved in aggressive schizophrenic patients.
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PMID:Association study of MAO-A and DRD4 genes in schizophrenic patients with aggressive behavior. 1765 71

The human monoamine oxidase A gene (MAOA) has attracted considerable attention as a candidate gene for schizophrenia based both on its chromosomal position and its enzyme function as a key factor in neurotransmitter catabolism pathways. However studies to date have reported inconsistent findings regarding the association between the variable number tandem repeat (VNTR) and T941G polymorphisms and schizophrenia. In an attempt to clarify this inconsistency we conducted a meta-analysis based on both alleles and genotypes (up to February 2006). In this study, however, we found no significant evidence of association with the two schizophrenia susceptibility polymorphisms.
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PMID:Meta-study on association between the monoamine oxidase A gene (MAOA) and schizophrenia. 1789 8

Many neurobiochemical studies show abnormalities within dopaminergic neuropathways, particularly altered dopamine transmission in etiopathogenesis of mental disorders. Evaluation of genes associated with the dopaminergic system include five well known subtypes of dopaminergic receptors, dopamine transporter and enzymes associated with the synthesis and degradation of dopamine, such as tyrosine hydroxylase, dopa decarboxylase, monoamine oxidase (MAO) and catechol O-methyltransferase (COMT). None of these genes is 'a' pathognomonic factor of schizophrenia onset. In each sequence of the following genes 'a' functional polymorphism can occur. The polymorphisms of genes MAO-A and COMT have been described in relation to various expression or altered activity of these enzymes, their influence on cognitive functions, affective and anxiety disorders, learning disabilities, aggressive behaviour, eating disorders or gender differences.
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PMID:[Genetic polymorphism of COMT in mental disorders]. 1804 78

Amin oxydase (monoaminoxydase, MAO) is an enzyme which catalyses chemical reactions of biogenic amines. It plays a crucial role in pathogenesis of mental disorders associated with the dysfunction of the central monoaminergic systems (schizophrenia, affective disorders, some forms of alcohol dependence, and personality disorders). MAO has got two isoforms such as MAO-A and MAO-B. The genes coding of MAO are localised at the short arm of chromosome Xp11. In each sequence of genes there is a probability of functional polymorphism occurrence which leads to a variable expression or a change of MAO activity and it exerts an impact on the onset of some mental disorders, such as: schizophrenia, affective disorders, some forms of alcohol dependence, and personality and behavioural disorders. Dynamic development of psychiatric genetics may have crucial impact on considerable progress in understanding molecular background of mental disorders.
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PMID:[Genetic polymorphism of a MAO in mental disorders]. 1804 79

Although there is evidence to link schizophrenia (SCZ) and bipolar disorder (BD) to genetic and environmental factors, specific individual or groups of genes/factors causative of the disease have been elusive to the research community. An understanding of the molecular aberrations that cause these mental illnesses requires comprehensive approaches that examine both genetic and epigenetic factors. Because of the overwhelming evidence for the role of environmental factors in the disease presentation, our initial approach involved deciphering how epigenetic changes resulting from promoter DNA methylation affect gene expression in SCZ and BD. Apparently, the central reversible but covalent epigenetic modification to DNA is derived from methylation of the cytosine residues that is potentially heritable and can affect gene expression and downstream activities. Environmental factors can influence DNA methylation patterns and hence alter gene expression. Such changes can be especially problematic in individuals with genetic susceptibilities to specific diseases. Recent reports from our laboratory provided compelling evidence that both hyper- and hypo-DNA methylation changes of the regulatory regions play critical roles in defining the altered functionality of genes in major psychiatric disorders such as SCZ and BD. In this chapter, we outline the technical details of the methods that could help to expand this line of research to assist with compiling the differential methylation-mediated epigenetic alterations that are responsible for the pathogenesis of SCZ, BD, and other mental diseases. We use the genes of the extended dopaminergic (DAergic) system such as membrane-bound catechol-O-methyltransferase (MB-COMT), monoamine oxidase A (MAOA), dopamine transporter 1 (DAT1), tyrosine hydroxylase (TH), dopamine (DA) receptors1 and 2 (DRD1/2), and related genes (e.g., reelin [RELN] and brain-derived neurotrophic factor [BDNF]) to illustrate the associations between differential promoter DNA methylations and disease phenotype. It is our hope that comprehensive analyses of the DAergic system as the prototype could provide the impetus and molecular basis to uncover early markers for diagnosis, help in the understanding of differences in disease severity in individuals with similar or identical genetic makeup, and assist with the identification of novel targets for therapeutic applications.
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PMID:Epigenetic alterations of the dopaminergic system in major psychiatric disorders. 1837 Feb 35

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


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