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)

At the X chromosome workshop of the Sixth World Congress on Psychiatric Genetics, new data regarding psychiatric phenotypes and the X chromosome were presented. In the last year a number of groups have published linkage results for the X chromosome in schizophrenia, which provide no significant evidence for linkage. Presentations by groups from Cardiff, Oxford, State University of New York (SUNY), and Finland provide weak nonsignificant evidence for linkage of markers on the Xp11.4-p11.3, Xq21, and Xq26 with schizophrenia. However, the presence of a male-specific transmission ratio distorter (DMS1) that maps to Xp11.4-21.2 [Naumova et al., 1998: Am. J. Hum. Genet. 62:1493-1499] makes the interpretation of linkage findings in brother-brother pairs difficult in this region. Regarding bipolar affective disorder, little new data were reported, but previous reports provide evidence for linkage to Xq25-q26. Summary tables of linkage results for schizophrenia and bipolar disorder can be obtained from http://www.camh.net/ research/x-chromosome/. No linkage or transmission disequilibrium of polymorphisms of MAOA and MAOB in attention deficit hyperactivity disorder was seen. Negative results for transmission disequilibrium of polymorphisms of HTR2C and MAOA with autism were provided from German and Austrian families.
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PMID:Sixth World Congress of Psychiatric Genetics X Chromosome Workshop. 1037 46

Serotonin (5-hydroxytryptamine, 5-HT) appears to play a role in the pathophysiology of a range of neuropsychiatric disorders, and serotonergic agents are of central importance in neuropharmacology. Genes encoding various components of the 5-HT system are being studied as risk factors in depression, schizophrenia, obsessive-compulsive disorder, aggression, alcoholism, and autism. Recently, pharmacogenetic research has begun to examine possible genetic influences on therapeutic response to drugs affecting the serotonin system. Genes regulating the synthesis (TPH), storage (VMAT2), membrane uptake (HTT), and metabolism (MAOA) of 5-HT, as well as a number of 5-HT receptors (HTR1A, HTR1B, HTR2A, HTR2C, and HTR5A), have been studied and this initial research is reviewed here. After a brief introduction to serotonin neurobiology and a general discussion of appropriate genetic methodology, each of the major 5-HT-related genes and their encoded proteins are reviewed in turn. For each gene, relevant polymorphisms and research on functional variants are discussed; following brief reviews of the disorder or trait association and linkage studies, pharmacogenetic studies performed to date are covered. The critical and manifold roles of the serotonin system, the great abundance of targets within the system, the wide range of serotonergic agents-available and in development-and the promising preliminary results suggest that the serotonin system offers a particularly rich area for pharmacogenetic research.
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PMID:Pharmacogenetics and the serotonin system: initial studies and future directions. 1113 68

Serotonergic pathways have been implicated in impulsive and aggressive behavior. Polymorphisms in the regulatory region of the serotonin transporter (5-HTT), in intron 7 of the tryptophan hydroxylase (TPH) gene and in the MAOA gene were previously reported to be associated with mood and anxiety disorders, impulsivity and aggression. In this study, we analyzed these polymorphisms in men and women with schizophrenia or schizoaffective disorder (n = 84) who met our criteria for violence (history of two or more assaults on others) or nonviolence (no history of either assaultive or threatening behavior). In males, a modest association between TPH genotype and history of violence (chi-square test = 6.703, degrees of freedom = 2, P = 0.035) was not statistically significant after correction for multiple comparisons (corrected P = 0.21). The TPH L allele was more frequent in violent males (chi-square = 5.323, degrees of freedom = 1, P = 0.021) but this difference also failed to withstand correction (corrected P = 0.126). No significant associations were found for either the 5-HTT or MAOA polymorphisms in males or females. These results tend to support previous reports by New et al. (1996; 1998) of an association between the TPH L allele and impulsive aggression in males with personality disorder, but larger studies are needed.
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PMID:An association between a polymorphism of the tryptophan hydroxylase gene and aggression in schizophrenia and schizoaffective disorder. 1120 46

Several lines of evidence suggest that psychosis is associated with altered dopaminergic neurotransmission. Dopamine is catabolized by monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT). We hypothesized that the genes encoding MAOA and COMT might contain genetic variation conferring increased risk to schizophrenia. In order to test this hypothesis, we genotyped the 941T > G and the promoter VNTR polymorphisms in the MAOA gene and the V158M COMT polymorphism in 346 DSMIV schizophrenics and 334 controls. We also genotyped the-287A > G COMT promoter polymorphism in 177 schizophrenics and 173 controls. No significant differences were found in allele or genotype frequencies between affecteds and controls for any of the polymorphisms. As both 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 genetic variation in MAOA and COMT is involved individually or in combination in the etiology of schizophrenia.
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PMID:Schizophrenia and functional polymorphisms in the MAOA and COMT genes: no evidence for association or epistasis. 1211 82

Some studies have reported associations between COMT and MAO genotypes and aggression, though results have been inconsistent. We examined the relationship between Overt aggression scale (OAS) scores, and both MAOA and MAOB polymorphisms in a well-powered sample of 346 subjects with schizophrenia. We also examined COMT in a Stage II replication sample of 150 individuals, and combined these results with our previously reported (Stage I) findings for COMT. We found no evidence of any associations between OAS ratings and any of the polymorphisms investigated under different genetic models. There was no evidence of epistatic interaction between MAOA and COMT on OAS scores. These results fail to support the theory that functional polymorphisms within the MAOA, MAOB, or COMT genes, as determinants of catecholamine enzymatic activity, are risk factors for aggressive behavior.
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PMID:Polymorphisms in the MAOA, MAOB, and COMT genes and aggressive behavior in schizophrenia. 1521 23

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

Monoamine oxidase (MAO) A is a critical enzyme in the catabolism of dopamine. Dysfunction of dopaminergic systems has been implicated in the pathophysiology of schizophrenia, suggesting that MAOA gene variation might be associated with the disorder. MAOA gene variation was compared between 234 Chinese schizophrenic patients and 121 healthy controls. Three polymorphic markers of the MAOA gene were analyzed using PCR techniques: two MAOA restriction fragment length polymorphisms (RFLP), -941G/T and -1460C/T, and the variable number tandem repeats (VNTR) in the promoter region. Linkage disequilibrium and haplotype analyses were performed with Bonferroni correction for multiple testing. In single marker analyses the 941T allele was significantly associated with schizophrenia in men (p=0.01). Haplotype analyses revealed a significant overall difference (p=0.03) between schizophrenia and control men, with higher frequencies of haplotypes containing the major allele (T) of -941T/G and the short allele (3 repeats) of the VNTR polymorphisms. No significant associations were detected for females using single markers or haplotypes. These findings suggest that genetic variants in MAOA may play a role in susceptibility to schizophrenia in Chinese men.
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PMID:Association between monoamine oxidase (MAO)-A gene variants and schizophrenia in a Chinese population. 1957 21

It is now generally accepted that complex mental disorders are the results of interplay between genetic and environmental factors. This holds out the prospect that by studying G x E interplay we can explain individual variation in vulnerability and resilience to environmental hazards in the development of mental disorders. Furthermore studying G x E findings may give insights in neurobiological mechanisms of psychiatric disorder and so improve individualized treatment and potentially prevention. In this paper, we provide an overview of the state of field with regard to G x E in mental disorders. Strategies for G x E research are introduced. G x E findings from selected mental disorders with onset in childhood or adolescence are reviewed [such as depressive disorders, attention-deficit/hyperactivity disorder (ADHD), obesity, schizophrenia and substance use disorders]. Early seminal studies provided evidence for G x E in the pathogenesis of depression implicating 5-HTTLPR, and conduct problems implicating MAOA. Since then G x E effects have been seen across a wide range of mental disorders (e.g., ADHD, anxiety, schizophrenia, substance abuse disorder) implicating a wide range of measured genes and measured environments (e.g., pre-, peri- and postnatal influences of both a physical and a social nature). To date few of these G x E effects have been sufficiently replicated. Indeed meta-analyses have raised doubts about the robustness of even the most well studied findings. In future we need larger, sufficiently powered studies that include a detailed and sophisticated characterization of both phenotype and the environmental risk.
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PMID:From nature versus nurture, via nature and nurture, to gene x environment interaction in mental disorders. 2002 96

Apoptosis has been considered to be involved in schizophrenia. Water channels are modulated just before apoptosis. In the aquaporin family, aquaporin 4 (AQP-4) is most highly expressed in the brain and is supposed to play an important role in a neuronal environment. In this clinical study, we investigated the relationship between the AQP-4 polymorphism and drug response in schizophrenia under the control of the MAOA (monoamine oxidase A) promoter gene. We recruited 91 patients with schizophrenia, and they were randomized to receive olanzapine (n = 44), risperidone (n = 23), or paliperidone (n = 24). Genotyping of AQP-4 and MAOA polymorphisms was done in all patients. Patients with the AQP-4 non-C polymorphism needed a higher dosage of olanzapine for treatment (z = 4.163, P = 0.041), and patients with a short form of the MAOA polymorphism needed a higher dosage of risperidone for treatment (z = 5.124, P = 0.024). Patients who smoked cigarettes needed a higher dosage of olanzapine for treatment (z = 4.905, P = 0.027), but cigarette smoking did not affect the dosage of paliperidone. The AQP-4 polymorphism may have an effect in influencing the dosage of olanzapine. However, the roles of AQP-4 polymorphisms in the blood-brain barrier and different neuroprotective effects need further exploration in future studies.
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PMID:Different impacts of aquaporin 4 and MAOA allele variation among olanzapine, risperidone, and paliperidone in schizophrenia. 2254 10

The concept of schizotypy or "psychosis proneness" captures individual differences in perceptual, cognitive, and affective experiences that may relate to a range of psychotic disorders. The concept is an important way to assess the contribution of pre-existing psychological and genetically based biological features to the development of illnesses such as schizophrenia (so called endophenotypes). The Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE) is a widely used multi-dimensional measure of the construct and consists of four scales which mirror several groups of psychotic symptoms: Unusual Experiences (UnEx; positive symptoms), Cognitive Disorganization (CogDis; cognitive symptoms), Introvertive Anhedonia (IntAn; negative symptoms), and Impulsive Nonconformity (ImpNon; impulsive and antisocial symptoms). For the purpose of evaluating the suitability of schizotypy as an endophenotype of schizophrenia the current version of the O-LIFE was translated into German: its psychometric properties (including re-test reliability and construct validity) were examined in a large sample (n > 1200) and compared to those of the English original. The German version was both highly reliable and consistent with the original. The study aimed to show that schizotypy as measured by the O-LIFE can indeed be regarded as an endophenotype of schizophrenia in terms of genetic associations regarding relevant dopamine-related candidate polymorphisms of schizotypy [i.e., Val(158)Met-polymorphism of the COMT gene, uVNTR of the MAOA gene, Taq1A-polymorphism of the DRD2 gene, VNTR of the SLC6A3 (DAT) gene]. We also wanted to compare the genetic associations of the O-LIFE to those published using other operationalizations of schizotypy. Our results show a large number of significant associations and borderline-significant trends between the O-LIFE sub-scales and a range of genes, thereby supporting using the O-LIFE in the search for endophenotypic markers.
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PMID:Dopaminergic foundations of schizotypy as measured by the German version of the Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE)-a suitable endophenotype of schizophrenia. 2335 17


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