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Sample records for comt val158 met

  1. COMT Val158Met Polymorphism Modulates Huntington's Disease Progression

    Science.gov (United States)

    Rebeix, Isabelle; Dupoux, Emmanuel; Durr, Alexandra; Brice, Alexis; Charles, Perrine; Cleret de Langavant, Laurent; Youssov, Katia; Verny, Christophe; Damotte, Vincent; Azulay, Jean-Philippe; Goizet, Cyril; Simonin, Clémence; Tranchant, Christine; Maison, Patrick; Rialland, Amandine; Schmitz, David; Jacquemot, Charlotte; Fontaine, Bertrand; Bachoud-Lévi, Anne-Catherine

    2016-01-01

    Little is known about the genetic factors modulating the progression of Huntington’s disease (HD). Dopamine levels are affected in HD and modulate executive functions, the main cognitive disorder of HD. We investigated whether the Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene, which influences dopamine (DA) degradation, affects clinical progression in HD. We carried out a prospective longitudinal multicenter study from 1994 to 2011, on 438 HD gene carriers at different stages of the disease (34 pre-manifest; 172 stage 1; 130 stage 2; 80 stage 3; 17 stage 4; and 5 stage 5), according to Total Functional Capacity (TFC) score. We used the Unified Huntington’s Disease Rating Scale to evaluate motor, cognitive, behavioral and functional decline. We genotyped participants for COMT polymorphism (107 Met-homozygous, 114 Val-homozygous and 217 heterozygous). 367 controls of similar ancestry were also genotyped. We compared clinical progression, on each domain, between groups of COMT polymorphisms, using latent-class mixed models accounting for disease duration and number of CAG (cytosine adenine guanine) repeats. We show that HD gene carriers with fewer CAG repeats and with the Val allele in COMT polymorphism displayed slower cognitive decline. The rate of cognitive decline was greater for Met/Met homozygotes, which displayed a better maintenance of cognitive capacity in earlier stages of the disease, but had a worse performance than Val allele carriers later on. COMT polymorphism did not significantly impact functional and behavioral performance. Since COMT polymorphism influences progression in HD, it could be used for stratification in future clinical trials. Moreover, DA treatments based on the specific COMT polymorphism and adapted according to disease duration could potentially slow HD progression. PMID:27657697

  2. COMT Val158Met Genotype as a Risk Factor for Problem Behaviors in Youth

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    Albaugh, Matthew D.; Harder, Valerie S.; Althoff, Robert R.; Rettew, David C.; Ehli, Erik A.; Lengyel-Nelson, Timea; Davies, Gareth E.; Ayer, Lynsay; Sulman, Julie; Stanger, Catherine; Hudziak, James J.

    2010-01-01

    Objective: To test the association between the catechol-O-methyltransferase (COMT) Val158Met polymorphism and both aggressive behavior and attention problems in youth. We hypothesized that youth carrying a Met allele would have greater average aggressive behavior scores, and that youth exhibiting Val-homozygosity would have greater average…

  3. COMT Val158Met genotypes differentially influence subgenual cingulate functional connectivity in healthy females

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    Chris eBaeken

    2014-06-01

    Full Text Available Brain imaging studies have consistently shown subgenual Anterior Cingulate Cortical (sgACC involvement in emotion processing. COMT Val158 and Met158 polymorphisms may influence such emotional brain processes in specific ways. Given that resting-state fMRI (rsfMRI may increase our understanding on brain functioning, we integrated genetic and rsfMRI data and focused on sgACC functional connections. No studies have yet investigated the influence of the COMT Val158Met polymorphism (rs4680 on sgACC resting-state functional connectivity (rsFC in healthy individuals. A homogeneous group of sixty-one Caucasian right-handed healthy female university students, all within the same age range, underwent rsfMRI. Compared to Met158 homozygotes, Val158 allele carriers displayed significantly stronger rsFC between the sgACC and the left parahippocampal gyrus, ventromedial parts of the inferior frontal gyrus, and the nucleus accumbens (NAc. On the other hand, compared to Val158 homozygotes, we found in Met158 allele carriers stronger sgACC rsFC with the medial frontal gyrus, more in particular the anterior parts of the medial orbitofrontal cortex. Although we did not use emotional or cognitive tasks, our sgACC rsFC results point to possible distinct differences in emotional and cognitive processes between Val158 and Met158 allele carriers. However, the exact nature of these directions remains to be determined.

  4. COMT val(158)met genotype and smooth pursuit eye movements in schizophrenia

    DEFF Research Database (Denmark)

    Haraldsson, H Magnus; Ettinger, Ulrich; Magnusdottir, Brynja B;

    2009-01-01

    The association between the catechol-O-methyltransferase (COMT) val(158)met polymorphism (rs4680) and smooth pursuit eye movements (SPEM) was investigated in 110 schizophrenia patients and 96 controls. Patients had lower steady-state pursuit gain and made more frequent saccades than controls...

  5. The roles of COMT val158met status and aviation expertise in flight simulator performance and cognitive ability.

    Science.gov (United States)

    Kennedy, Q; Taylor, J L; Noda, A; Adamson, M; Murphy, G M; Zeitzer, J M; Yesavage, J A

    2011-09-01

    The polymorphic variation in the val158met position of the catechol-O-methyltransferase (COMT) gene is associated with differences in executive performance, processing speed, and attention. The purpose of this study is: (1) replicate previous COMT val158met findings on cognitive performance; (2) determine whether COMT val158met effects extend to a real-world task, aircraft navigation performance in a flight simulator; and (3) determine if aviation expertise moderates any effect of COMT val158met status on flight simulator performance. One hundred seventy two pilots aged 41-69 years, who varied in level of aviation training and experience, completed flight simulator, cognitive, and genetic assessments. Results indicate that although no COMT effect was found for an overall measure of flight performance, a positive effect of the met allele was detected for two aspects of cognitive ability: executive functioning and working memory performance. Pilots with the met/met genotype benefited more from increased levels of expertise than other participants on a traffic avoidance measure, which is a component of flight simulator performance. These preliminary results indicate that COMT val158met polymorphic variation can affect a real-world task.

  6. No association between Val158Met of the COMT gene and susceptibility to schizophrenia in the Syrian population

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    Bassam Lajin

    2011-01-01

    Full Text Available Background : The Val158Met single nucleotide polymorphism of the COMT gene has been implicated in the aetiology of schizophrenia, although results from different populations have been conflicting. Aims: The aim of the present study was to investigate possible association between schizophrenia and Val158Met in a novel Arab population from Syria. Methods and Materials: 71 unrelated schizophrenic subjects (45 men and 102 unrelated healthy controls (62 men were recruited to take part in this case- control study. The Val158Met of the COMT gene was genotyped for patients and controls, using a new optimized PCR-RFLP method. Results: the results demonstrated that there is no statistically significant difference between the two groups. Conclusion: This study does not support that Val158Met has an influence on susceptibility for schizophrenia in this population.

  7. Val158Met COMT polymorphism and risk of aggression in alcohol dependence.

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    Soyka, Michael; Zill, Peter; Koller, Gabi; Samochowiec, Agnieszka; Grzywacz, Anna; Preuss, Ulrich W

    2015-01-01

    Aggression, violence and antisocial behavior are common in alcoholism, but their biological basis is poorly understood. Several studies and recent meta-analyses indicate that in schizophrenia the catecholamine-O-methyltransferase (COMT) Val158Met genotype may be associated with aggression, most often in methionine allele carriers. We tested this hypothesis in a sample of treatment-seeking alcohol-dependent in-patients (293 German patients and 499 controls, and additional 190 Polish patients as replication sample). As expected, patients with a history of violent or non-violent crime were more often male, had an earlier onset of alcoholism and more withdrawal seizures and delirium tremens, and were more likely to have a history of suicide attempts. COMT genotype was not associated with a history of violent or non-violent crime. More studies are needed on the neurobiological basis of aggression and violence in alcoholism.

  8. Daytime sleepiness and the COMT val158met polymorphism in patients with Parkinson disease.

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    Rissling, Ida; Frauscher, Birgit; Kronenberg, Florian; Tafti, Mehdi; Stiasny-Kolster, Karin; Robyr, Anne-Catherine; Körner, Yvonne; Oertel, Wolfgang Hermann; Poewe, Werner; Högl, Birgit; Möller, Jens Carsten

    2006-01-01

    A preliminary study by our group suggested an association between daytime sleepiness and the catechol-O-methyltransferase (COMT) val158met polymorphism (rs4680) in patients with Parkinson disease (PD). We sought to confirm this association in a large group of patients with PD. Genetic association study in patients with PD. Movement disorder sections at 2 university hospitals. PD patients with and without episodes of suddenly falling asleep matched for antiparkinsonian medication, disease duration, sex, and age, who participated in a previous genetic study on dopamine-receptor polymorphisms. Not applicable. In this study, 240 patients with PD (154 men; age 65.1 +/- 6.1 years; disease duration 9.4 +/- 6.0 years) were included. Seventy had the met-met (LL), 116 the met-val (LH), and 54 the val-val (HH) genotype. In the combined LL+LH group (featuring reduced COMT activity), the mean Epworth Sleepiness Scale (ESS) score was 9.0 +/- 5.9 versus 11.0 +/- 6.1 in the HH (high COMT activity) group (P = .047). Forty-seven percent of the LL and LH patients had sudden sleep onset compared with 61% of the HH patients (P = .07). Logistic regression, however, showed that both pathologic ESS scores (i.e., > 10) and sudden sleep onset were predicted by subjective disease severity (P < .001 each) but not by the COMT genotype. Our previous finding that the L-allele may be associated with daytime sleepiness could not be confirmed in the present study. Altogether, our data do not support a clinically relevant effect of the COMT genotype on daytime sleepiness in PD.

  9. A meta-analysis of the Val158Met COMT polymorphism and violent behavior in schizophrenia.

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    Jay P Singh

    Full Text Available We conducted a meta-analysis of studies examining the association between the Val158Met COMT polymorphism and violence against others in schizophrenia. A systematic search current to November 1, 2011 was conducted using MEDLINE, EMBASE, CINAHL, PsycINFO, ProQuest, and the National Criminal Justice Reference Service and identified 15 studies comprising 2,370 individuals with schizophrenia for inclusion. Bivariate analyses of study sensitivities and specificities were conducted. This methodology allowed for the calculation of pooled diagnostic odds ratios (DOR. Evidence of a significant association between the presence of a Met allele and violence was found such that men's violence risk increased by approximately 50% for those with at least one Met allele compared with homozygous Val individuals (DOR = 1.45; 95% CI = 1.05-2.00; z = 2.37, p = 0.02. No significant association between the presence of a Met allele and violence was found for women or when outcome was restricted to homicide. We conclude that male schizophrenia patients who carry the low activity Met allele in the COMT gene are at a modestly elevated risk of violence. This finding has potential implications for the pharmacogenetics of violent behavior in schizophrenia.

  10. Association between the Catechol O-methyltransferase (COMT Val158met polymorphism and different dimensions of impulsivity.

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    Leandro Fernandes Malloy-Diniz

    Full Text Available BACKGROUND: Impulsivity is a multidimensional construct which has been associated with dopaminergic neurotransmission. Nonetheless, until this moment, few studies addressed the relationship between different types of impulsivity and the single nucleotide polymorphism caused by a substitution of valine (val with methionine (met in the 158 codon of the Catechol-o-Methyltransferase gene (COMT-val158met. The present study aimed to investigate the association between val158met COMT polymorphism and impulsive behavior measured by two neuropsychological tests. METHODOLOGY/PRINCIPAL FINDINGS: We administered two neuropsychological tests, a Continuous Performance Task and the Iowa Gambling Task were applied to 195 healthy participants to characterize their levels of motor, attentional and non-planning impulsivity. Then, subjects were grouped by genotype, and their scores on impulsivity measures were compared. There were no significant differences between group scores on attentional and motor impulsivity. Those participants who were homozygous for the met allele performed worse in the Iowa Gambling Task than val/val and val/met subjects. CONCLUSIONS/SIGNIFICANCE: Our results suggest that met allele of val158met COMT polymorphism is associated with poor performance in decision-making/cognitive impulsivity task. The results reinforce the hypothesis that val and met alleles of the val158met polymorphism show functional dissociation and are related to different prefrontal processes.

  11. Effect of COMT Val158Met polymorphism on personality traits and educational attainment in a longitudinal population representative study.

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    Lehto, K; Akkermann, K; Parik, J; Veidebaum, T; Harro, J

    2013-10-01

    The COMT Val158Met polymorphism has been associated with anxiety and affective disorders, but its effect on anxiety-related personality traits varies between studies. Our purpose was to investigate the effect of COMT Val158Met on personality traits from adolescence to young adulthood in a population representative Caucasian birth cohort. Also its association with educational attainment and anxiety and mood disorders by the age 25 were examined. This analysis is based on the older cohort of the Estonian Children Personality Behavior and Health Study (original number of subjects 593). The personality traits were assessed when the participants were 15, 18 and 25 years old. COMT Val158Met had an effect on Neuroticism in females by age 25 (p=0.001, Bonferroni-corrected for five traits), whereas female Val homozygotes scored the highest. In addition, the Conscientiousness scores of subjects with Val/Val genotype were decreasing in time, being the lowest by the age 25 (p=0.006, Bonferroni-corrected for five traits). By the age 25, males with the Val/Met genotype had mainly secondary or vocational education, whereas female heterozygotes mostly had obtained or were obtaining university education. COMT Val158Met was not associated with anxiety or mood disorders in either gender. These results suggest that genes affecting dopamine system are involved in the development of personality traits and contribute to educational attainment.

  12. Differential Association of the COMT Val158Met Polymorphism with Clinical Phenotypes in Schizophrenia and Bipolar Disorder

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    Goghari, Vina M.; Sponheim, Scott R.

    2008-01-01

    Schizophrenia and bipolar disorder, although diagnostically separate, likely share elements of their genetic etiology. This study assessed whether COMT Val158Met polymorphism has shared or specific associations with clinical phenotypes evident in schizophrenia and bipolar disorder. Schizophrenia and bipolar patients completed a clinical assessment encompassing premorbid functioning and current and lifetime symptomatology. Multivariate analyses yielded a three-way interaction of diagnosis, COM...

  13. Influence of COMT val158met Genotype on the Depressed Brain during Emotional Processing and Working Memory

    NARCIS (Netherlands)

    Opmeer, Esther M.; Kortekaas, Rudie; van Tol, Marie-Jose; van der Wee, Nic J. A.; Woudstra, Saskia; van Buchem, Mark A.; Penninx, Brenda W.; Veltman, Dick J.; Aleman, Andre

    2013-01-01

    Major depressive disorder (MDD) has been associated with abnormal prefrontal-limbic interactions and altered catecholaminergic neurotransmission. The val158met polymorphism on the catechol-O-methyltransferase (COMT) gene has been shown to influence prefrontal cortex (PFC) activation during both emot

  14. Differential association of the COMT Val158Met polymorphism with clinical phenotypes in schizophrenia and bipolar disorder.

    Science.gov (United States)

    Goghari, Vina M; Sponheim, Scott R

    2008-08-01

    Schizophrenia and bipolar disorder, although diagnostically separate, likely share elements of their genetic etiology. This study assessed whether the COMT Val158Met polymorphism has shared or specific associations with clinical phenotypes evident in schizophrenia and bipolar disorder. Schizophrenia and bipolar patients completed a clinical assessment encompassing premorbid functioning and current and lifetime symptomatology. Multivariate analyses yielded a three-way interaction of diagnosis, COMT genotype for lifetime symptomatology. The COMT Val allele was associated with greater positive symptomatology in schizophrenia, whereas Met homozygosity was associated with greater positive symptomatology in bipolar disorder. Findings support the COMT Val158Met polymorphism conferring vulnerability for different clinical phenotypes in schizophrenia and bipolar disorder. Lifetime symptomatology may be particularly useful in determining the relationship between genes and clinical phenotypes across mental disorders.

  15. COMT Val158Met and PPARγ Pro12Ala polymorphisms and susceptibility to Alzheimer's disease: a meta-analysis.

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    Lee, Young Ho; Song, Gwan Gyu

    2014-05-01

    The aim of this study was to explore whether the catechol-O-methyltransferase (COMT) Val158Met or the peroxisome proliferator-activated receptor-gamma (PPARγ) Pro12Ala polymorphisms are associated with susceptibility to Alzheimer's disease (AD). We conducted a meta-analysis of the associations between the COMT Val158Met and the PPARγ Pro12Ala polymorphisms and AD in subjects. Meta-analysis showed no association between AD and the COMT G allele in any of the study subjects [odds ratio (OR) = 0.972, 95 % confidence intervals (95 % CI) = 0.893-1.059, p = 0.515]. Stratification by ethnicity indicated an association between the COMT GG+GA genotype and AD in an Asian group (OR = 0.702, 95 % CI = 0.517-0.953, p = 0.023), but not in Europeans (OR = 1.058, 95 % CI = 0.868-1.289, p = 0.579). Homozygote contrast analysis showed the same pattern for the COMT GG+GA genotype. Meta-analysis showed no association between AD and the PPARγ polymorphism (OR for the C allele = 0.963, 95 % CI = 0.818-1.134, p = 0.649). This meta-analysis identified an association between AD and the COMT Val158Met polymorphism in Asians but not in Europeans, but it revealed no association between AD and the PPARγ Pro12Ala polymorphism.

  16. Interaction between COMT Val(158)Met polymorphism and childhood adversity affects reward processing in adulthood.

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    Boecker-Schlier, Regina; Holz, Nathalie E; Buchmann, Arlette F; Blomeyer, Dorothea; Plichta, Michael M; Jennen-Steinmetz, Christine; Wolf, Isabella; Baumeister, Sarah; Treutlein, Jens; Rietschel, Marcella; Meyer-Lindenberg, Andreas; Banaschewski, Tobias; Brandeis, Daniel; Laucht, Manfred

    2016-05-15

    Accumulating evidence suggests that altered dopamine transmission may increase the risk of mental disorders such as ADHD, schizophrenia or depression, possibly mediated by reward system dysfunction. This study aimed to clarify the impact of the COMT Val(158)Met polymorphism in interaction with environmental variation (G×E) on neuronal activity during reward processing. 168 healthy young adults from a prospective study conducted over 25years participated in a monetary incentive delay task measured with simultaneous EEG-fMRI. DNA was genotyped for COMT, and childhood family adversity (CFA) up to age 11 was assessed by a standardized parent interview. At reward delivery, a G×E revealed that fMRI activation for win vs. no-win trials in reward-related regions increased with the level of CFA in Met homozygotes as compared to Val/Met heterozygotes and Val homozygotes, who showed no significant effect. During the anticipation of monetary vs. verbal rewards, activation decreased with the level of CFA, which was also observed for EEG, in which the CNV declined with the level of CFA. These results identify convergent genetic and environmental effects on reward processing in a prospective study. Moreover, G×E effects during reward delivery suggest that stress during childhood is associated with higher reward sensitivity and reduced efficiency in processing rewarding stimuli in genetically at-risk individuals. Together with previous evidence, these results begin to define a specific system mediating interacting effects of early environmental and genetic risk factors, which may be targeted by early intervention and prevention. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. COMT Val158Met polymorphism interacts with stressful life events and parental warmth to influence decision making

    OpenAIRE

    Qinghua He; Gui Xue; Chuansheng Chen; Zhong-Lin Lu; Chunhui Chen; Xuemei Lei; Yuyun Liu; Jin Li; Bi Zhu; Moyzis, Robert K.; Qi Dong; Antoine Bechara

    2012-01-01

    Both genetic and environmental factors have been shown to influence decision making, but their relative contributions and interactions are not well understood. The present study aimed to reveal possible gene-environment interactions on decision making in a large healthy sample. Specifically, we examined how the frequently studied COMT Val158Met polymorphism interacted with an environmental risk factor (i.e., stressful life events) and a protective factor (i.e., parental warmth) to influence a...

  18. Influence of COMT val158met genotype on the depressed brain during emotional processing and working memory.

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    Esther M Opmeer

    Full Text Available Major depressive disorder (MDD has been associated with abnormal prefrontal-limbic interactions and altered catecholaminergic neurotransmission. The val158met polymorphism on the catechol-O-methyltransferase (COMT gene has been shown to influence prefrontal cortex (PFC activation during both emotional processing and working memory (WM. Although COMT-genotype is not directly associated with MDD, it may affect MDD pathology by altering PFC activation, an endophenotype associated with both COMT and MDD. 125 participants, including healthy controls (HC, n=28 and MDD patients were genotyped for the COMT val158met polymorphism and underwent functional magnetic resonance imaging (fMRI-neuroimaging during emotion processing (viewing of emotional facial expressions and a WM task (visuospatial planning. Within HC, we observed a positive correlation between the number of met-alleles and right inferior frontal gyrus activation during emotional processing, whereas within patients the number of met-alleles was not correlated with PFC activation. During WM a negative correlation between the number of met-alleles and middle frontal gyrus activation was present in the total sample. In addition, during emotional processing there was an effect of genotype in a cluster including the amygdala and hippocampus. These results demonstrate that COMT genotype is associated with relevant endophenotypes for MDD. In addition, presence of MDD only interacts with genotype during emotional processing and not working memory.

  19. Modulation of the COMT Val158Met polymorphism on resting-state EEG power in postmenopausal healthy women

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    Silvia eSolis-Ortiz

    2015-04-01

    Full Text Available The catechol-O-methyltransferase (COMT Val158Met polymorphism impacts cortical dopamine levels and may influence cortical electrical activity in the human brain. This study investigated whether COMT genotype influences resting-state electroencephalogram (EEG power in the frontal, parietal and midline regions in healthy volunteers. EEG recordings were conducted in the resting-state in 13 postmenopausal healthy woman carriers of the Val/Val genotype and 11 with the Met/Met genotype. The resting EEG spectral absolute power in the frontal (F3, F4, F7, F8, FC3 and FC4, parietal (CP3, CP4, P3 and P4 and midline (Fz, FCz, Cz, CPz, Pz and Oz was analyzed during the eyes-open and eyes-closed conditions. The frequency bands considered were the delta, theta, alpha1, alpha2, beta1 and beta2. EEG data of the Val/Val and Met/Met genotypes, brain regions and conditions were analyzed using a general linear model analysis. In the individuals with the Met/Met genotype, delta activity was increased in the eyes-closed condition, theta activity was increased in the eyes-closed and in the eyes-open conditions, and alpha1 band, alpha2 band and beta1band activity was increased in the eyes-closed condition.A significant interaction between COMT genotypes and spectral bands was observed. Met homozygote individuals exhibited more delta, theta and beta1 activity than individuals with the Val/Val genotype. No significant interaction between COMT genotypes and the resting-state EEG regional power and conditions were observed for the three brain regions studied. Our findings indicate that the COMT Val158Met polymorphism does not directly impact resting-state EEG regional power, but instead suggest that COMT genotype can modulate resting-state EEG spectral power in postmenopausal healthy women.

  20. 儿童攻击行为与COMT Val158Met及5-HTTLPR基因多态性关联分析%Association between aggressive behaviors and COMT Val158Met and 5-HTTLPR polymorphisms in children

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    曹玉萍; 李龙飞; 赵幸福; 张亚林

    2011-01-01

    目的 探讨儿茶酚胺氧位甲基转移酶(COMT)第158位密码子从缬氨酸到蛋氨酸的错义突变(Val158Met)多态性及5-羟色胺转运体(5-HTT)基因启动子区缺失/插入多态性(5-HTTLPR)是否为家庭暴力环境下儿童攻击行为的易感因素.方法 以家庭暴力环境下68例儿童作为研究对象,依据Achenbach儿童行为量表(父母卷)评分,其中24例为攻击行为高分组,44例为低分组.采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)技术,检测两组COMT Val158Met和5-HTTLPR多态性,对所得基因型和等位基因频率进行对照和关联分析.结果 攻击行为高分组与低分组COMT Val158Met多态性的各基因型差异(χ2=1.612,P=0.447)和等位基因频率差异(χ2=1.648,P=0.119)均无统计学意义.两组5-HTTLPR多态性的各基因型差异(χ2=1.807,P=0.405)和等位基因频率差异(χ2=0.403,P=0.527)亦无统计学意义.结论 本研究结果不支持COMT Val158Met和5-HTTLPR基因多态性是儿童攻击行为产生的易感因素.提示儿童攻击行为可能是多因素共同作用的结果.%Objective To investigate the association between aggressive behaviors and catechol-O-methyltransferase (COMT) single nucleotide polymorphism at position 158 from a valine to a methionine (Val158Met) as well as serotonin (5-HT) transporter gene linked polymorphic region (5-HTTLPR) in children. Methods A total of 68 children who were exposed to domestic violence were recruited. The frequencies of genotypes and alleles of COMT Val158Met and 5-HTTLPR were examined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. A comparison was conducted between 24 children with high scores of aggressive problems and 44 control children with low scores of aggressive problems according to Child Behavior Checklist ( for parents). Results There were no significant differences in genotypes of C OMT Vail 58Met (x2 = 1.612,P = 0. 447) and 5-HTTLPR (x2

  1. Relationship between the COMT-Val158Met and BDNF-Val66Met polymorphisms, childhood trauma and psychotic experiences in an adolescent general population sample.

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    Hugh Ramsay

    Full Text Available OBJECTIVE: Psychotic experiences occur at a much greater prevalence in the population than psychotic disorders. There has been little research to date, however, on genetic risk for this extended psychosis phenotype. We examined whether COMT or BDNF genotypes were associated with psychotic experiences or interacted with childhood trauma in predicting psychotic experiences. METHOD: Psychiatric interviews and genotyping for COMT-Val158Met and BDNF-Val66Met were carried out on two population-based samples of 237 individuals aged 11-15 years. Logistic regression was used to examine for main effects by genotype and childhood trauma, controlling for important covariates. This was then compared to a model with a term for interaction between genotype and childhood trauma. Where a possible interaction was detected, this was further explored in stratified analyses. RESULTS: While childhood trauma showed a borderline association with psychotic experiences, COMT-Val158Met and BDNF-Val66Met genotypes were not directly associated with psychotic experiences in the population. Testing for gene x environment interaction was borderline significant in the case of COMT-Val158Met with individuals with the COMT-Val158Met Val-Val genotype, who had been exposed to childhood trauma borderline significantly more likely to report psychotic experiences than those with Val-Met or Met-Met genotypes. There was no similar interaction by BDNF-Val66Met genotype. CONCLUSION: The COMT-Val158Met Val-Val genotype may be a genetic moderator of risk for psychotic experiences in individuals exposed to childhood traumatic experiences.

  2. COMT Val158Met Polymorphism, Executive Dysfunction, and Sexual Risk Behavior in the Context of HIV Infection and Methamphetamine Dependence

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    C. A. Bousman

    2010-01-01

    Full Text Available Catechol-O-methyltransferease (COMT metabolizes prefrontal cortex dopamine (DA, a neurotransmitter involved in executive behavior; the Val158Met genotype has been linked to executive dysfunction, which might increase sexual risk behaviors favoring HIV transmission. Main and interaction effects of COMT genotype and executive functioning on sexual risk behavior were examined. 192 sexually active nonmonogamous men completed a sexual behavior questionnaire, executive functioning tests, and were genotyped using blood-derived DNA. Main effects for executive dysfunction but not COMT on number of sexual partners were observed. A COMT x executive dysfunction interaction was found for number of sexual partners and insertive anal sex, significant for carriers of the Met/Met and to a lesser extent Val/Met genotypes but not Val/Val carriers. In the context of HIV and methamphetamine dependence, dopaminergic overactivity in prefrontal cortex conferred by the Met/Met genotype appears to result in a liability for executive dysfunction and potentially associated risky sexual behavior.

  3. The catechol-O-methyltransferase (COMT val158met polymorphism affects brain responses to repeated painful stimuli.

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    Marco L Loggia

    Full Text Available Despite the explosion of interest in the genetic underpinnings of individual differences in pain sensitivity, conflicting findings have emerged for most of the identified "pain genes". Perhaps the prime example of this inconsistency is represented by catechol-O-methyltransferase (COMT, as its substantial association to pain sensitivity has been reported in various studies, but rejected in several others. In line with findings from behavioral studies, we hypothesized that the effect of COMT on pain processing would become apparent only when the pain system was adequately challenged (i.e., after repeated pain stimulation. In the present study, we used functional Magnetic Resonance Imaging (fMRI to investigate the brain response to heat pain stimuli in 54 subjects genotyped for the common COMT val158met polymorphism (val/val = n 22, val/met = n 20, met/met = n 12. Met/met subjects exhibited stronger pain-related fMRI signals than val/val in several brain structures, including the periaqueductal gray matter, lingual gyrus, cerebellum, hippocampal formation and precuneus. These effects were observed only for high intensity pain stimuli after repeated administration. In spite of our relatively small sample size, our results suggest that COMT appears to affect pain processing. Our data demonstrate that the effect of COMT on pain processing can be detected in presence of 1 a sufficiently robust challenge to the pain system to detect a genotype effect, and/or 2 the recruitment of pain-dampening compensatory mechanisms by the putatively more pain sensitive met homozygotes. These findings may help explain the inconsistencies in reported findings of the impact of COMT in pain regulation.

  4. No evidence of association between Catechol-O-Methyltransferase (COMT Val158Met genotype and performance on neuropsychological tasks in children with ADHD: A case-control study

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    O'Donovan Michael C

    2004-06-01

    Full Text Available Abstract Background Several studies have suggested an association between the functional Val158Met polymorphism in the Catechol-O-Methyltransferase (COMT gene and neurocognitive performance. Two studies showed that subjects with the low activity Met allele performed better on the Wisconsin Card Sorting Test (WCST and another study found an effect on processing speed and attention. Methods We set out to examine the association between the Val158Met polymorphism and performance on neurocognitive tasks including those tapping working memory, attention and speed, impulsiveness and response inhibition in a sample of 124 children with ADHD. Task performance for each genotypic group was compared using analysis of variance. Results There was no evidence of association with performance on any of the neurocognitive tasks. Conclusions We conclude that Val158Met COMT genotype is not associated with neurocognitive performance in our sample.

  5. No association between COMT val158met polymorphism and suicidal behavior: meta-analysis and new data

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    Genis Mendoza Alma D

    2011-09-01

    Full Text Available Abstract Background The polymorphism COMTval158met has been associated with suicidal behavior in case-control and meta-analysis studies, but results and conclusions remain controversial. The objective of this study was to examine the association between COMT val158met with suicidal behavior in a case-control study and to assess the combined evidence -this case-control study and available data from other related studies- we carried out a meta-analysis. Methods We conducted a case-control study with 105 patients with suicide attempts and 236 controls. Subsequently, we performed a meta-analysis of published genetic association studies by searching through Medline, PubMed and Web of Science databases. Results No significant differences were found in the distribution of alleles (χ2 = 0.33, 1 df, p = 0.56 or genotypes (χ2 = 2.36, 2 df, p = 0.26. The meta-analysis comprising 12 association studies (including the present one showed that the risk COMTmet allele of COMTval158/met is not associated with suicidal behavior (OR: 1.09, 95% CI: 0.97-1.23, even in the absence of heterogeneity (OR: 1.09, 95% CI: 0.97-1.23. Conclusion Our results showed no association between COMTval158/met and suicidal behavior. However, more studies are necessary to determine conclusively an association between COMT and suicidal behavior.

  6. COMT Val158Met polymorphism is associated with blood pressure and lipid levels in general families of Bama longevous area in China.

    Science.gov (United States)

    Ge, Lin; Wu, Hua-Yu; Pan, Shang-Ling; Huang, Ling; Sun, Peng; Liang, Qing-Hua; Pang, Guo-Fang; Lv, Ze-Ping; Hu, Cai-You; Liu, Cheng-Wu; Zhou, Xiao-Ling; Huang, Ling-Jin; Yin, Rui-Xing; Peng, Jun-Hua

    2015-01-01

    To see the possible relationship between COMT Val158Met polymorphism and blood pressure (BP) and serum lipid levels and its putative role in human longevity, we genotyped COMT Val158Met (rs4680) by PCR-RFLP for members from Bama long-lived families (BLF, n = 1538), Bama non-long-lived families (BNLF, n = 600), Pingguo (a county outside Bama region) long-lived families (PLF, n = 538) and Pingguo non-long-lived families (PNLF, n = 403) after anthropometric measures were collected and serum lipid levels were detected. The distribution of genotypes and alleles among four family groups was significantly different (all P pressure (SBP), pulse pressure (PP), total cholesterol (TC), triglyceride (TG) and low density lipoprotein-cholesterol (LDL-C) levels of GG genotype carriers were dramatically higher than non-GG carriers in BNLF (P pressure and lipids were observed between genotypes in BLF and PNLF (P > 0.05). Correlation analyses revealed that COMT Val158Met was mainly correlated negatively with SBP, diastolic blood pressure (DBP) and LDL-C in BNLF and negatively with TC level in BLF, BNLF and PLF. These data suggest that COMT Val158Met polymorphism may have more impact on the modulation of BP and lipid profiles in the average families than in the long-lived families in Bama region. The association between this SNP and other phenotypes (e.g. cognition) and its roles in the longevity in Bama area thus warrant further investigation.

  7. The interaction of early life experiences with COMT val158met affects anxiety sensitivity.

    Science.gov (United States)

    Baumann, C; Klauke, B; Weber, H; Domschke, K; Zwanzger, P; Pauli, P; Deckert, J; Reif, A

    2013-11-01

    The pathogenesis of anxiety disorders is considered to be multifactorial with a complex interaction of genetic factors and individual environmental factors. Therefore, the aim of this study was to examine gene-by-environment interactions of the genes coding for catechol-O-methyltransferase (COMT) and monoamine oxidase A (MAOA) with life events on measures related to anxiety. A sample of healthy subjects (N = 782; thereof 531 women; mean age M = 24.79, SD = 6.02) was genotyped for COMT rs4680 and MAOA-uVNTR (upstream variable number of tandem repeats), and was assessed for childhood adversities [Childhood Trauma Questionnaire (CTQ)], anxiety sensitivity [Anxiety Sensitivity Index (ASI)] and anxious apprehension [Penn State Worry Questionnaire (PSWQ)]. Main and interaction effects of genotype, environment and gender on measures related to anxiety were assessed by means of regression analyses. Association analysis showed no main gene effect on either questionnaire score. A significant interactive effect of childhood adversities and COMT genotype was observed: Homozygosity for the low-active met allele and high CTQ scores was associated with a significant increment of explained ASI variance [R(2) = 0.040, false discovery rate (FDR) corrected P = 0.04]. A borderline interactive effect with respect to MAOA-uVNTR was restricted to the male subgroup. Carriers of the low-active MAOA allele who reported more aversive experiences in childhood exhibited a trend for enhanced anxious apprehension (R(2) = 0.077, FDR corrected P = 0.10). Early aversive life experiences therefore might increase the vulnerability to anxiety disorders in the presence of homozygosity for the COMT 158met allele or low-active MAOA-uVNTR alleles.

  8. Association between the COMT Val158Met polymorphism and risk of cancer: evidence from 99 case–control studies

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    Zhou Q

    2015-10-01

    Full Text Available Quan Zhou, Yan Wang, Aihua Chen, Yaling Tao, Huamei Song, Wei Li, Jing Tao, Manzhen ZuoDepartment of Gynecology and Obstetrics, The People’s Hospital of Three Gorges University, The First People’s Hospital of Yichang, Yichang, People’s Republic of ChinaAbstract: Catechol-O-methyltransferase (COMT plays a central role in DNA repair and estrogen-induced carcinogenesis. Many recent epidemiologic studies have investigated the association between the COMT Val158Met polymorphism and cancer risk, but the results are inconclusive. In this study, we performed a meta-analysis to investigate the association between cancer susceptibility and COMT Val158Met in different genetic models. Overall, no significant associations were found between COMT Val158Met polymorphism and cancer risk (homozygote model: odds ratio [OR] =1.05, 95% confidence interval [CI] = [0.98, 1.13]; heterozygote model: OR =1.01, 95% CI = [0.98, 1.04]; dominant model: OR =1.02, 95% CI [0.97, 1.06], and recessive model: OR =1.03, 95% CI [0.97, 1.09]. In the subgroup ­analysis of cancer type, COMT Val158Met was significantly associated with increased risks of ­bladder cancer in recessive model, and esophageal cancer in homozygote model, heterozygote model, and dominant model. Subgroup analyses based on ethnicities, COMT Val158Met was significantly associated with increased risk of cancer in homozygote and recessive model among Asians. In addition, homozygote, recessive, and dominant models were significantly associated with increased cancer risk in the subgroup of allele-specific polymerase chain reaction genotyping. Significant associations were not observed when data were stratified by the source of the controls. In summary, this meta-analysis suggested that COMT Val158Met polymorphism might not be a risk factor for overall cancer risk, but it might be involved in cancer development at least in some ethnic groups (Asian or some specific cancer types (bladder and esophageal cell

  9. COMT Val158Met polymorphism interacts with stressful life events and parental warmth to influence decision making.

    Science.gov (United States)

    He, Qinghua; Xue, Gui; Chen, Chuansheng; Lu, Zhong-Lin; Chen, Chunhui; Lei, Xuemei; Liu, Yuyun; Li, Jin; Zhu, Bi; Moyzis, Robert K; Dong, Qi; Bechara, Antoine

    2012-01-01

    Both genetic and environmental factors have been shown to influence decision making, but their relative contributions and interactions are not well understood. The present study aimed to reveal possible gene-environment interactions on decision making in a large healthy sample. Specifically, we examined how the frequently studied COMT Val(158)Met polymorphism interacted with an environmental risk factor (i.e., stressful life events) and a protective factor (i.e., parental warmth) to influence affective decision making as measured by the Iowa Gambling Task. We found that stressful life events acted as a risk factor for poor IGT performance (i.e., high reward sensitivity) among Met carriers, whereas parental warmth acted as a protective factor for good IGT performance (i.e., higher IGT score) among Val/Val homozygotes. These results shed some new light on gene-environment interactions in decision making, which could potentially help us understand the underlying etiology of several psychiatric disorders associated with decision making impairment.

  10. COMT Val 158 Met polymorphism is associated with nonverbal cognition following mild traumatic brain injury

    NARCIS (Netherlands)

    E.A. Winkler (Ethan A.); J.K. Yue (John); T.W. McAllister (Thomas W.); N.R. Temkin (Nancy); S.S. Oh (Sam S.); E.G. Burchard (Esteban); D. Hu (Donglei); A.R. Ferguson (Adam); H.F. Lingsma (Hester); J.F. Burke (John F.); M.D. Sorani (Marco); J. Rosand (Jonathan); E.L. Yuh (Esther); J. Barber (Jason); P.E. Tarapore (Phiroz E.); R.C. Gardner (Raquel C.); S. Sharma (Sourabh); G.G. Satris (Gabriela G.); C. Eng (Celeste); A.M. Puccio (Ava); K.K.W. Wang (Kevin K. W.); P. Mukherjee (Pratik); A.B. Valadka (Alex); D. Okonkwo (David); R. Diaz-Arrastia (Ramon); G. Manley (Geoffrey)

    2016-01-01

    textabstractMild traumatic brain injury (mTBI) results in variable clinical outcomes, which may be influenced by genetic variation. A single-nucleotide polymorphism in catechol-o-methyltransferase (COMT), an enzyme which degrades catecholamine neurotransmitters, may influence cognitive deficits foll

  11. COMT Val 158 Met polymorphism is associated with nonverbal cognition following mild traumatic brain injury

    NARCIS (Netherlands)

    E.A. Winkler (Ethan A.); J.K. Yue (John); T.W. McAllister (Thomas W.); N.R. Temkin (Nancy); S.S. Oh (Sam S.); E.G. Burchard (Esteban); D. Hu (Donglei); A.R. Ferguson (Adam); H.F. Lingsma (Hester); J.F. Burke (John F.); M.D. Sorani (Marco); J. Rosand (Jonathan); E.L. Yuh (Esther); J. Barber (Jason); P.E. Tarapore (Phiroz E.); R.C. Gardner (Raquel C.); S. Sharma (Sourabh); G.G. Satris (Gabriela G.); C. Eng (Celeste); A.M. Puccio (Ava); K.K.W. Wang (Kevin K. W.); P. Mukherjee (Pratik); A.B. Valadka (Alex); D. Okonkwo (David); R. Diaz-Arrastia (Ramon); G. Manley (Geoffrey)

    2016-01-01

    textabstractMild traumatic brain injury (mTBI) results in variable clinical outcomes, which may be influenced by genetic variation. A single-nucleotide polymorphism in catechol-o-methyltransferase (COMT), an enzyme which degrades catecholamine neurotransmitters, may influence cognitive deficits

  12. Increased sensitivity to thermal pain following a single opiate dose is influenced by the COMT val(158met polymorphism.

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    Karin B Jensen

    Full Text Available Increased pain sensitivity after opioid administration (opioid-induced hyperalgesia and/or repeated painful stimuli is an individually varying and clinically important phenomenon. The functional polymorphism (val(158met of the Catechol-O-methyltransferase (COMT gene regulates the metabolism of dopamine/noradrenaline. Individuals homozygous for the met(158 allele have been reported to have increased pain sensitivity and there are findings of lower micro-opioid system activation during sustained pain. We hypothesized that met/met individuals would exhibit higher pain sensitization and opioid-induced hyperalgesia in response to repeated pain stimuli and an intravenous injection of an opioid drug. Participants were 43 healthy subjects who went through an experiment where five blocks of pain were induced to the hand using a heat probe. After each stimulus subjects rated the pain on a visual analogue scale (VAS from 0 mm (no pain to 100 mm (worst possible pain. Before the second stimulus there was an intravenous injection of a rapid and potent opioid drug. At baseline there was no difference in pain ratings between the COMTval(158met genotypes, F(2, 39<1. However, a repeated measures ANOVA for all five stimuli revealed a main effect for COMTval(158met genotype, F(2, 36 = 4.17, p = 0.024. Met/met individuals reported significantly more pain compared to val/val, p = 0.010. A pairwise comparison of baseline and the opioid intervention demonstrated that analgesia was induced in all groups (p = 0.042 without a separating effect for genotype (n.s. We suggest that the initial response of the descending pain system is not influenced by the COMTval(158met polymorphism but when the system is challenged the difference is revealed. An important clinical implication of this may be that the COMTval(158met related differences may be more expressed in individuals where the inhibitory system is already challenged and sensitive, e.g. chronic pain patients. This has to

  13. The val158met polymorphism of human catechol-O-methyltransferase (COMT affects anterior cingulate cortex activation in response to painful laser stimulation

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    Musso Francesco

    2010-05-01

    Full Text Available Abstract Background Pain is a complex experience with sensory, emotional and cognitive aspects. Genetic and environmental factors contribute to pain-related phenotypes such as chronic pain states. Genetic variations in the gene coding for catechol-O-methyltransferase (COMT have been suggested to affect clinical and experimental pain-related phenotypes including regional μ-opioid system responses to painful stimulation as measured by ligand-PET (positron emission tomography. The functional val158met single nucleotide polymorphism has been most widely studied. However, apart from its impact on pain-induced opioid release the effect of this genetic variation on cerebral pain processing has not been studied with activation measures such as functional magnetic resonance imaging (fMRI, PET or electroencephalography. In the present fMRI study we therefore sought to investigate the impact of the COMT val158met polymorphism on the blood oxygen level-dependent (BOLD response to painful laser stimulation. Results 57 subjects were studied. We found that subjects homozygous for the met158 allele exhibit a higher BOLD response in the anterior cingulate cortex (ACC, foremost in the mid-cingulate cortex, than carriers of the val158 allele. Conclusion This result is in line with previous studies that reported higher pain sensitivity in homozygous met carriers. It adds to the current literature in suggesting that this behavioral phenotype may be mediated by, or is at least associated with, increased ACC activity. More generally, apart from one report that focused on pain-induced opioid release, this is the first functional neuroimaging study showing an effect of the COMT val158met polymorphism on cerebral pain processing.

  14. COMT Val(158) met genotype and striatal D(2/3) receptor binding in adults with 22q11 deletion syndrome.

    LENUS (Irish Health Repository)

    Boot, Erik

    2011-09-01

    Although catechol-O-methyltransferase (COMT) activity evidently affects dopamine function in prefrontal cortex, the contribution is assumed less significant in striatum. We studied whether a functional polymorphism in the COMT gene (Val(158) Met) influences striatal D(2\\/3) R binding ratios (D(2\\/3) R BP(ND) ) in 15 adults with 22q11 deletion syndrome and hemizygous for this gene, using single photon emission computed tomography and the selective D(2\\/3) radioligand [(123) I]IBZM. Met hemizygotes had significantly lower mean D(2\\/3) R BPND than Val hemizygotes. These preliminary data suggest that low COMT activity may affect dopamine levels in striatum in humans and this may have implications for understanding the contribution of COMT activity to psychiatric disorders.

  15. COMT Val(158)Met polymorphism is associated with post-traumatic stress disorder and functional outcome following mild traumatic brain injury.

    Science.gov (United States)

    Winkler, Ethan A; Yue, John K; Ferguson, Adam R; Temkin, Nancy R; Stein, Murray B; Barber, Jason; Yuh, Esther L; Sharma, Sourabh; Satris, Gabriela G; McAllister, Thomas W; Rosand, Jonathan; Sorani, Marco D; Lingsma, Hester F; Tarapore, Phiroz E; Burchard, Esteban G; Hu, Donglei; Eng, Celeste; Wang, Kevin K W; Mukherjee, Pratik; Okonkwo, David O; Diaz-Arrastia, Ramon; Manley, Geoffrey T

    2017-01-01

    Mild traumatic brain injury (mTBI) results in variable clinical trajectories and outcomes. The source of variability remains unclear, but may involve genetic variations, such as single nucleotide polymorphisms (SNPs). A SNP in catechol-o-methyltransferase (COMT) is suggested to influence development of post-traumatic stress disorder (PTSD), but its role in TBI remains unclear. Here, we utilize the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study to investigate whether the COMT Val(158)Met polymorphism is associated with PTSD and global functional outcome as measured by the PTSD Checklist - Civilian Version and Glasgow Outcome Scale Extended (GOSE), respectively. Results in 93 predominately Caucasian subjects with mTBI show that the COMT Met(158) allele is associated with lower incidence of PTSD (univariate odds ratio (OR) of 0.25, 95% CI [0.09-0.69]) and higher GOSE scores (univariate OR 2.87, 95% CI [1.20-6.86]) 6-months following injury. The COMT Val(158)Met genotype and PTSD association persists after controlling for race (multivariable OR of 0.29, 95% CI [0.10-0.83]) and pre-existing psychiatric disorders/substance abuse (multivariable OR of 0.32, 95% CI [0.11-0.97]). PTSD emerged as a strong predictor of poorer outcome on GOSE (multivariable OR 0.09, 95% CI [0.03-0.26]), which persists after controlling for age, GCS, and race. When accounting for PTSD in multivariable analysis, the association of COMT genotype and GOSE did not remain significant (multivariable OR 1.73, 95% CI [0.69-4.35]). Whether COMT genotype indirectly influences global functional outcome through PTSD remains to be determined and larger studies in more diverse populations are needed to confirm these findings.

  16. COMT Val158Met polymorphism influences the susceptibility to framing in decision-making: OFC-amygdala functional connectivity as a mediator.

    Science.gov (United States)

    Gao, Xiaoxue; Gong, Pingyuan; Liu, Jinting; Hu, Jie; Li, Yue; Yu, Hongbo; Gong, Xiaoliang; Xiang, Yang; Jiang, Changjun; Zhou, Xiaolin

    2016-05-01

    Individuals tend to avoid risk in a gain frame, in which options are presented in a positive way, but seek risk in a loss frame, in which the same options are presented negatively. Previous studies suggest that emotional responses play a critical role in this "framing effect." Given that the Met allele of COMT Val158Met polymorphism (rs4680) is associated with the negativity bias during emotional processing, this study investigated whether this polymorphism is associated with individual susceptibility to framing and which brain areas mediate this gene-behavior association. Participants were genotyped, scanned in resting state, and completed a monetary gambling task with options (sure vs risky) presented as potential gains or losses. The Met allele carriers showed a greater framing effect than the Val/Val homozygotes as the former gambled more than the latter in the loss frame. Moreover, the gene-behavior association was mediated by resting-state functional connectivity (RSFC) between orbitofrontal cortex (OFC) and bilateral amygdala. Met allele carriers showed decreased RSFC, thereby demonstrating higher susceptibility to framing than Val allele carriers. These findings demonstrate the involvement of COMT Val158Met polymorphism in the framing effect in decision-making and suggest RSFC between OFC and amygdala as a neural mediator underlying this gene-behavior association. Hum Brain Mapp 37:1880-1892, 2016. © 2016 Wiley Periodicals, Inc.

  17. Neonatal pain and COMT Val158Met genotype in relation to serotonin transporter (SLC6A4 promoter methylation in very preterm children at school age

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    Cecil Ming Yeung Chau

    2014-12-01

    Full Text Available Children born very preterm are exposed to repeated neonatal procedures that induce pain and stress during hospitalization in the neonatal intensive care unit (NICU. The COMT Val158Met genotype is involved with pain sensitivity, and early life stress is implicated in altered expression of methylation of the serotonin transporter. We examined: (1 whether methylation of the serotonin transporter gene (SLC6A4 promoter differs between very preterm children and full-term controls at school age, (2 relationships with child behavior problems, and (3 whether the extent of neonatal pain exposure interacts with the COMT Val158Met genotype to predict SLC6A4 methylation at 7 years in the very preterm children. We examined the associations between the COMT genotypes, neonatal pain exposure (adjusted for neonatal clinical confounders, SLC6A4 methylation and behavior problems. Very preterm children had significantly higher methylation at 7/10 CpG sites in the SLC6A4 promoter compared to full-term controls at 7 years. Neonatal pain (adjusted for clinical confounders was significantly associated with total child behaviour problems on the Child Behavior Checklist (CBCL questionnaire (adjusted for concurrent stressors and 5HTTLPR genotype (p = 0.035. CBCL total problems was significantly associated with greater SLC6A4 methylation in very preterm children (p = 0.01. Neonatal pain (adjusted for clinical confounders and COMT Met/Met genotype were associated with SLC6A4 promoter methylation in very preterm children at 7 years (p = 0.001. These findings provide evidence that both genetic predisposition and early environment need to be considered in understanding susceptibility for developing behavioral problems in this vulnerable population.

  18. Association of the Catechol-O-Methyltransferase (COMT) Val158Met Polymorphism and Anxiety-Related Traits: A Meta-Analysis

    Science.gov (United States)

    Lee, Lewina O.; Prescott, Carol A.

    2014-01-01

    Objectives The main goals of this study were: (i) to examine genotypic association of the COMT val158met polymorphism with anxiety-related traits via a meta-analysis; (ii) to examine sex and ethnicity as moderators of the association, and (iii) to evaluate whether the association differed by particular anxiety traits. Methods Association studies of the COMT val18met polymorphism and anxiety traits were identified from the PubMed or PsycInfo databases, conference abstracts and listserv postings. Exclusion criteria were: (a) pediatric samples, (b) exclusively clinical samples, and (c) samples selected for a non-anxiety phenotype. Standardized mean differences in anxiety between genotypes were aggregated to produce mean effect sizes across all available samples, and for subgroups stratified by sex and ethnicity (Caucasians vs. Asians). Construct-specific analysis was conducted to evaluate the association of COMT with neuroticism, harm avoidance, and behavioral inhibition. Results Twenty seven eligible studies (N=15,979) with available data were identified. Overall findings indicate sex-specific and ethnic-specific effects: Val homozygotes had higher neuroticism than Met homozygotes in studies of Caucasian males ( ES¯=0.13, 95%CI: 0.02 – 0.25, p = 0.03), and higher harm avoidance in studies of Asian males ( ES¯=0.43, 95%CI: 0.14 – 0.72, p = 0.004). No significant associations were found in women and effect sizes were diminished when studies were aggregated across ethnicity or anxiety traits. Conclusions: This meta-analysis provides evidence for sex and ethnicity differences in the association of the COMT val158met polymorphism with anxiety traits. Our findings contribute to current knowledge on the relation between prefrontal dopaminergic transmission and anxiety. PMID:24300663

  19. Epistasis between COMT Val158Met and DRD3 Ser9Gly polymorphisms and cognitive function in schizophrenia: genetic influence on dopamine transmission

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    Alexandre A. Loch

    2015-09-01

    Full Text Available Objective:To assess the relationship between cognitive function, a proposed schizophrenia endophenotype, and two genetic polymorphisms related to dopamine function, catechol-O-methyl transferase (COMT Val158Met and dopamine receptor 3 (DRD3 Ser9Gly.Methods:Fifty-eight outpatients with schizophrenia/schizoaffective disorder and 88 healthy controls underwent neurocognitive testing and genotyping. Analyses of covariance (ANCOVAs using age, sex, and years of education as covariates compared cognitive performance for the proposed genotypes in patients and controls. ANCOVAs also tested for the epistatic effect of COMT and DRD3 genotype combinations on cognitive performance.Results:For executive functioning, COMT Val/Val patients performed in a similar range as controls (30.70-33.26 vs. 35.53-35.67, but as COMT Met allele frequency increased, executive functioning worsened. COMT Met/Met patients carrying the DRD3 Ser/Ser genotype performed poorest (16.184 vs. 27.388-31.824. Scores of carriers of this COMT/DRD3 combination significantly differed from all DRD3 Gly/Gly combinations (p < 0.05, from COMT Val/Met DRD3 Ser/Gly (p = 0.02, and from COMT Val/Val DRD3 Ser/Ser (p = 0.01 in patients. It also differed significantly from all control scores (p < 0.001.Conclusion:Combined genetic polymorphisms related to dopamine neurotransmission might influence executive function in schizophrenia. Looking at the effects of multiple genes on a single disease trait (epistasis provides a comprehensive and more reliable way to determine genetic effects on endophenotypes.

  20. Age-Dependent Effects of Catechol-O-Methyltransferase (COMT) Gene Val158Met Polymorphism on Language Function in Developing Children.

    Science.gov (United States)

    Sugiura, Lisa; Toyota, Tomoko; Matsuba-Kurita, Hiroko; Iwayama, Yoshimi; Mazuka, Reiko; Yoshikawa, Takeo; Hagiwara, Hiroko

    2016-11-30

    The genetic basis controlling language development remains elusive. Previous studies of the catechol-O-methyltransferase (COMT) Val(158)Met genotype and cognition have focused on prefrontally guided executive functions involving dopamine. However, COMT may further influence posterior cortical regions implicated in language perception. We investigated whether COMT influences language ability and cortical language processing involving the posterior language regions in 246 children aged 6-10 years. We assessed language ability using a language test and cortical responses recorded during language processing using a word repetition task and functional near-infrared spectroscopy. The COMT genotype had significant effects on language performance and processing. Importantly, Met carriers outperformed Val homozygotes in language ability during the early elementary school years (6-8 years), whereas Val homozygotes exhibited significant language development during the later elementary school years. Both genotype groups exhibited equal language performance at approximately 10 years of age. Val homozygotes exhibited significantly less cortical activation compared with Met carriers during word processing, particularly at older ages. These findings regarding dopamine transmission efficacy may be explained by a hypothetical inverted U-shaped curve. Our findings indicate that the effects of the COMT genotype on language ability and cortical language processing may change in a narrow age window of 6-10 years.

  1. The functional COMT polymorphism, Val 158 Met, is associated with logical memory and the personality trait intellect/imagination in a cohort of healthy 79 year olds.

    Science.gov (United States)

    Harris, Sarah E; Wright, Alan F; Hayward, Caroline; Starr, John M; Whalley, Lawrence J; Deary, Ian J

    2005-09-02

    A polymorphism (Val 158 Met) in the gene for catechol-O-methyl transferase (COMT) was previously associated with differences in cognitive ability and personality. Here we examine associations between this polymorphism and cognitive ability, cognitive aging, personality and mood in 460 relatively healthy people born in 1921. All had cognitive ability measured at age 11 in the Scottish Mental Survey of 1932, and again at age 79. COMT genotype was not associated with childhood IQ. At age 79, COMT genotype was significantly related to differences in verbal declarative memory (scores on the Logical Memory test; p=0.028) and to scores on the personality trait of intellect/imagination (p=0.023), adjusted for sex and childhood IQ. In both cases the Val/Met heterozygotes had higher scores than both homozygous groups. There were trends toward the heterozygotes having higher scores on the personality traits of agreeableness and conscientiousness. The effect of COMT genotype on Logical Memory scores was independent of the effect of APOE genotype, and similar in effect size. Therefore, COMT genotype may contribute to differences in normal cognitive aging and to differences in some of the major personality traits in old age.

  2. Association of COMT val158met and DRD2 G>T genetic polymorphisms with individual differences in motor learning and performance in female young adults.

    Science.gov (United States)

    Noohi, Fatemeh; Boyden, Nate B; Kwak, Youngbin; Humfleet, Jennifer; Burke, David T; Müller, Martijn L T M; Bohnen, Nico I; Seidler, Rachael D

    2014-02-01

    Individuals learn new skills at different rates. Given the involvement of corticostriatal pathways in some types of learning, variations in dopaminergic transmission may contribute to these individual differences. Genetic polymorphisms of the catechol-O-methyltransferase (COMT) enzyme and dopamine receptor D2 (DRD2) genes partially determine cortical and striatal dopamine availability, respectively. Individuals who are homozygous for the COMT methionine (met) allele show reduced cortical COMT enzymatic activity, resulting in increased dopamine levels in the prefrontal cortex as opposed to individuals who are carriers of the valine (val) allele. DRD2 G-allele homozygotes benefit from a higher striatal dopamine level compared with T-allele carriers. We hypothesized that individuals who are homozygous for COMT met and DRD2 G alleles would show higher rates of motor learning. Seventy-two young healthy females (20 ± 1.9 yr) performed a sensorimotor adaptation task and a motor sequence learning task. A nonparametric mixed model ANOVA revealed that the COMT val-val group demonstrated poorer performance in the sequence learning task compared with the met-met group and showed a learning deficit in the visuomotor adaptation task compared with both met-met and val-met groups. The DRD2 TT group showed poorer performance in the sequence learning task compared with the GT group, but there was no difference between DRD2 genotype groups in adaptation rate. Although these results did not entirely come out as one might predict based on the known contribution of corticostriatal pathways to motor sequence learning, they support the role of genetic polymorphisms of COMT val158met (rs4680) and DRD2 G>T (rs 1076560) in explaining individual differences in motor performance and motor learning, dependent on task type.

  3. Association between the Catechol-O-Methyltransferase (COMT) Val158Met Polymorphism and Manual Aiming Control in Healthy Subjects

    Science.gov (United States)

    Lage, Guilherme M.; Miranda, Débora M.; Romano-Silva, Marco A.; Campos, Simone B.; Albuquerque, Maicon R.; Corrêa, Humberto; Malloy-Diniz, Leandro F.

    2014-01-01

    Background Prefrontal dopamine is catabolized by the catechol-O-methyltransferase (COMT) enzyme. Current evidence suggests that the val/met single nucleotide polymorphism in the COMT gene can predict the efficiency of executive cognition in humans. Individuals carrying the val allele perform more poorly because less synaptic dopamine is available. Methodology/Principal Findings We investigated the influence of the COMT polymorphism on motor performance in a task that requires different executive functions. We administered a manual aiming motor task that was performed under four different conditions of execution by 111 healthy participants. Participants were grouped according to genotype (met/met, met/val, val/val), and the motor performance among groups was compared. Overall, the results indicate that met/met carriers presented lower levels of peak velocity during the movement trajectory than the val carriers, but met/met carriers displayed higher accuracy than the val carriers. Conclusions/Significance This study found a significant association between the COMT polymorphism and manual aiming control. Few studies have investigated the genetics of motor control, and these findings indicate that individual differences in motor control require further investigation using genetic studies. PMID:24956262

  4. COMT Val158Met genotype selectively alters prefrontal [18F]fallypride displacement and subjective feelings of stress in response to a psychosocial stress challenge.

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    Dennis Hernaus

    Full Text Available Catechol-O-methyltransferase (COMT plays an essential role in degradation of extracellular dopamine in prefrontal regions of the brain. Although a polymorphism in this gene, COMT Val(158Met, affects human behavior in response to stress little is known about its effect on dopaminergic activity associated with the human stress response, which may be of interest for stress-related psychiatric disorders such as psychosis. We aimed to investigate the effect of variations in COMT genotype on in vivo measures of stress-induced prefrontal cortex (PFC dopaminergic processing and subjective stress responses. A combined sample of healthy controls and healthy first-degree relatives of psychosis patients (n = 26 were subjected to an [(18F]fallypride Positron Emission Tomography scan. Psychosocial stress during the scan was induced using the Montreal Imaging Stress Task and subjective stress was assessed every 12 minutes. Parametric t-maps, generated using the linear extension of the simplified reference region model, revealed an effect of COMT genotype on the spatial extent of [(18F]fallypride displacement. Detected effects of exposure to psychosocial stress were unilateral and remained restricted to the left superior and right inferior frontal gyrus, with Met-hetero- and homozygotes showing less [(18F]fallypride displacement than Val-homozygotes. Additionally, Met-hetero- and homozygotes experienced larger subjective stress responses than Val-homozygotes. The direction of the effects remained the same when the data was analyzed separately for controls and first-degree relatives. The human stress response may be mediated in part by COMT-dependent dopaminergic PFC activity, providing speculation for the neurobiology underlying COMT-dependent differences in human behaviour following stress. Implications of these results for stress-related psychopathology and models of dopaminergic functioning are discussed.

  5. Functional COMT Val158Met polymorphism, risk of acute coronary events and serum homocysteine: the Kuopio ischaemic heart disease risk factor study.

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    Sari Voutilainen

    Full Text Available BACKGROUND: The role of circulating levels of total homocysteine tHcy in the development of coronary heart disease (CHD is still under debate. One reason for conflicting results between previous studies on homocysteine and heart diseases could be consequence of different interactions between homocysteine and genes in different study populations. Many genetic factors play a role in folate-homocysteine metabolism, like functional polymorphism (Val108Met in the Catechol-O-methyltransferase (COMT gene. METHODOLOGY AND FINDINGS: Our aim was to examine the role of COMT Val158Met polymorphism and interaction of this polymorphism with serum tHcy and folate concentration on the risk of acute coronary and events in middle-aged men from eastern Finland. A population-based prospective cohort of 792 men aged 46-64 years was examined as part of the Kuopio Ischaemic Heart Disease Risk Factor Study. During an average follow-up of 9.3 years, there were 69 acute coronary events in men with no previous history of CHD. When comparing the COMT low activity genotype with the others, we found an age and examination year adjusted hazard rate ratio (HRR of 1.73 (95% confidence interval (CI, 1.07-2.79, and an age, examination year, serum LDL and HDL cholesterol, and triglyceride concentration, systolic blood pressure and smoking adjusted HRR of 1.77 (95% CI, 1.05-2.77. Although serum tHcy concentration was not statistically significantly associated with acute coronary events (HRR for the highest third versus others 1.52, 95% CI, 0.93-2.49, subjects with both high serum tHcy and the COMT low activity genotype had an additionally increased adjusted risk of HRR 2.94 (95% CI 1.50-5.76 as compared with other men. CONCLUSIONS: This prospective cohort study suggests that the functional COMT Val158Met polymorphism is associated with increased risk of acute coronary events and it may interact with high serum tHcy levels.

  6. 长寿家系COMT Val158Met基因多态性及其与血压和血脂水平的相关性%Association of COMT Val158Met polymorphism with blood pressure and serum lipid levels in long-lived families

    Institute of Scientific and Technical Information of China (English)

    王艺苑; 庞国防; 罗桓; 胡才友; 潘尚领; 彭均华; 刘承武

    2015-01-01

    目的 探讨长寿家系COMT Val158Met(G>A)基因多态性与血压、血脂水平的相关性,了解其在长寿中的作用.方法 用PCR-RFLP方法对广西红水河流域长寿家系(HL)及非长寿家系(HNL)、外地区(平果)长寿(PL)及非长寿家系(PNL)的COMT Val158Met进行基因分型,分析该多态与血压和血脂水平的相关性.结果 等位基因A及其基因型(GA/AA)频率在HL和HNL间无差异,但高于PL和PNL(P <0.01).HL和PNL的血压、血脂水平在GA/AA和GG基因型携带者之间无差异,但HNL的GA/AA携带者的收缩压、脉压差、TC、TG及LDL-C水平明显高于GG携带者(P<0.05),尤以女性为甚,PL的部分结果与此类似.COMT Val158Met多态与HNL及PL的TC和LDL-C水平呈负相关(P< 0.05).结论 COMT Val158Met虽然在红水河流域人群中高频出现,但其对血压及血脂的影响主要在一般家系,对长寿家系的影响较小.

  7. Differential influence of 5-HTTLPR - polymorphism and COMT Val158Met - polymorphism on emotion perception and regulation in healthy women.

    Science.gov (United States)

    Weiss, Elisabeth M; Freudenthaler, H Harald; Fink, Andreas; Reiser, Eva M; Niederstätter, Harald; Nagl, Simone; Parson, Walther; Papousek, Ilona

    2014-05-01

    Converging evidence indicates that a considerable amount of variance in self-estimated emotional competency can be directly attributed to genetic factors. The current study examined the associations between the polymorphisms of the Catechol-O-methyltransferase (COMT Met158Val) and the serotonin transporter (5-HTTLPR) and specific measures of the self-estimated effectiveness of an individual's emotion perception and regulation. Emotional competence was measured in a large sample of 289 healthy women by using the Self-report Emotional Ability Scale (SEAS), which includes two subscales for the assessment of emotion perception and regulation in the intra-personal domain and two subscales for the assessment of emotion perception and regulation in the inter-personal domain. Participants' reports of effective emotion regulation in everyday life were associated with the COMT Met-allele, with women homozygous for the Val-allele scoring lowest on this scale. Self-estimated effectiveness of emotion perception of the individual's own emotions was related to the 5-HTTLPR. Both homozygous groups (s/s and l/l) rated their intra-personal emotion perception less effective than participants in the heterozygous s/l group. Taken together, the results indicate that genetic variants of the COMT and 5HTTLPR genes are differentially associated with specific measures of the self-estimated effectiveness of an individual's emotion perception and regulation in the intra-personal domain.

  8. Catechol-O-Methyltransferase gene val158met polymorphism and depressive symptoms during early childhood

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    Sheikh, Haroon I.; Kryski, Katie R.; Smith, Heather J.; Dougherty, Lea R.; Klein, Daniel N.; Bufferd, Sara J.; Singh, Shiva M.; Hayden, Elizabeth P.

    2017-01-01

    Catechol-O-Methyltransferase (COMT) is a critical regulator of catecholamine levels in the brain. A functional polymorphism of the COMT gene, val158met, has been linked to internalizing symptoms (i.e., depression and anxiety) in adolescents and adults. We extended this research by investigating whether the val158met polymorphism was associated with childhood symptoms of depression and anxiety in two independent samples of young children (Ns = 476 and 409). In both samples, preschool-aged children were genotyped for the COMT val158met polymorphism. Symptoms of psychopathology were assessed via parent interviews and primary caregiver reports. In both samples, children homozygous for the val allele had higher levels of depressive symptoms compared to children with at least one copy of the met allele. Our findings extend previous research in older participants by showing links between the COMT val158met polymorphism and internalizing symptoms in early childhood. PMID:23475824

  9. Lack of association of COMT Val158Met polymorphism with attention and executive function in patients with schizophrenia%精神分裂症COMT基因Val158Met多态性与注意力及执行功能缺乏关联

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    王强; 杨振兴; 梁林辉; 谷晓楚; 黄朝华; 李名立; 邓伟; 马小红; 王英成

    2014-01-01

    目的 探讨COMT基因Val158Met多态性与执行功能以及注意力之间的相关性.方法 采用连线测验评估103例精神分裂症患者(患者组)和99名正常对照(对照组)的注意力和执行功能;采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测COMT Val158 met各突变点的基因多态性并进行基因分型,用SPSS 13.0软件的一般线性模型分析COMT Val158Met多态性和执行功能以及注意力之间的相关性.结果 执行功能以及注意力在患者组和对照组中差异有统计学意义,而在三组基因型之间的差异无统计学意义.结论 COMT Val158Met多态性和执行功能以及注意力无相关性,主要原因可能是人群的异质性.%Objective To explore the association of a functional polymorphism Val158Met of COMT gene and attention and executive function in first-episode treatment-na(i)ve patients with schizophrenia and healthy controls.Method Trail making test (TMT) and clinical performances were evaluated in 103 firstepisode treatment-naive patients with schizophrenia and 99 healthy controls.Polymorphism of COMT Val158Met was analyzed using polymerase chain reaction-restriction fragment length polymorphism method.A general linear model was used to investigate the effect of genotype subgroups on the attention and executive function.Results There was a significant difference between control subjects and patients with schizophrenia on the TMT-A and B.However,no significant difference among Val/Val,Val/Met and Met/ Met on the TMT-A and B in control subjects and patients with schizophrenia was detected.Conclusion The association among COMTMet variant and trail making testing (attention and executive function) has been replicated.However,no association of COMTMet variant with disruption of dopaminergic influence on neurocognitive function was detected.This may be due to the heterogeneity of population.

  10. The catechol-O-methyltransferase (COMT) Val158Met genotype modulates working memory-related dorsolateral prefrontal response and performance in bipolar disorder

    DEFF Research Database (Denmark)

    Miskowiak, K W; Kjaerstad, H L; Støttrup, M M

    2017-01-01

    OBJECTIVES: Cognitive dysfunction affects a substantial proportion of patients with bipolar disorder (BD), and genetic-imaging paradigms may aid in the elucidation of mechanisms implicated in this symptomatic domain. The Val allele of the functional Val158Met polymorphism of the catechol-O-methyl...

  11. COMT Val158Met, but not BDNF Val66Met, is associated with white matter abnormalities of the temporal lobe in patients with first-episode, treatment-naïve major depressive disorder: a diffusion tensor imaging study

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    Hayashi K

    2014-06-01

    Full Text Available Kenji Hayashi,1 Reiji Yoshimura,1 Shingo Kakeda,2 Taro Kishi,3 Osamu Abe,4 Wakako Umene-Nakano,1 Asuka Katsuki,1 Hikaru Hori,1 Atsuko Ikenouchi-Sugita,1 Keita Watanabe,2 Satoru Ide,2 Issei Ueda,2 Junji Moriya,2 Nakao Iwata,3 Yukunori Korogi,2 Marek Kubicki,5 Jun Nakamura1 1Department of Psychiatry, 2Department of Radiology, University of Occupational and Environmental Health, Kitakyushu, Japan; 3Department of Psychiatry, Fujita Health University, Toyoake, Japan; 4Department of Radiology, Nihon University School of Medicine, Tokyo, Japan; 5Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Abstract: We investigated the association between the Val158Met polymorphism of the catechol-O-methyltransferase (COMT gene, the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF gene, and white matter changes in patients with major depressive disorder (MDD and healthy subjects using diffusion tensor imaging (DTI. We studied 30 patients with MDD (17 males and 13 females, with mean age ± standard deviation [SD] =44±12 years and 30 sex- and age-matched healthy controls (17 males and 13 females, aged 44±13 years. Using DTI analysis with a tract-based spatial statistics (TBSS approach, we investigated the differences in fractional anisotropy, radial diffusivity, and axial diffusivity distribution among the three groups (patients with the COMT gene Val158Met, those with the BDNF gene Val66Met, and the healthy subjects. In a voxel-wise-based group comparison, we found significant decreases in fractional anisotropy and axial diffusivity within the temporal lobe white matter in the Met-carriers with MDD compared with the controls (P<0.05. No correlations in fractional anisotropy, axial diffusivity, or radial diffusivity were observed between the MDD patients and the controls, either among those with the BDNF Val/Val genotype or among the BDNF Met-carriers. These results suggest an association

  12. White matter alterations related to attention-deficit hyperactivity disorder and COMT val158met polymorphism: children with valine homozygote attention-deficit hyperactivity disorder have altered white matter connectivity in the right cingulum (cingulate gyrus

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    Kabukcu Basay B

    2016-04-01

    Full Text Available Burge Kabukcu Basay,1 Ahmet Buber,1 Omer Basay,1 Huseyin Alacam,2 Onder Ozturk,1 Serkan Suren,3 Ozlem Izci Ay,4 Cengizhan Acikel,5 Kadir Agladioglu,6 Mehmet Emin Erdal,4 Eyup Sabri Ercan,7 Hasan Herken21Child and Adolescent Psychiatry Department, Pamukkale University Medical Faculty, Denizli, 2Psychiatry Department, Pamukkale University Medical Faculty, Denizli, 3Medical Park Samsun Hospital, Samsun, 4Medical Biology and Genetics Department, Mersin University Medical Faculty, Mersin, 5Biostatistics Department, GATA (GMMA, Ankara, 6Radiology Department, Pamukkale University Medical Faculty, Denizli, 7Child and Adolescent Psychiatry Department, Ege University Medical Faculty, Izmir, TurkeyIntroduction: In this article, the COMT gene val158met polymorphism and attention-deficit hyperactivity disorder (ADHD-related differences in diffusion-tensor-imaging-measured white matter (WM structure in children with ADHD and controls were investigated.Patients and methods: A total of 71 children diagnosed with ADHD and 24 controls aged 8–15 years were recruited. Using diffusion tensor imaging, COMT polymorphism and ADHD-related WM alterations were investigated, and any interaction effect between the COMT polymorphism and ADHD was also examined. The effects of age, sex, and estimated total IQ were controlled by multivariate analysis of covariance (MANCOVA.Results: First, an interaction between the COMT val158met polymorphism and ADHD in the right (R cingulum (cingulate gyrus (CGC was found. According to this, valine (val homozygote ADHD-diagnosed children had significantly lower fractional anisotropy (FA and higher radial diffusivity (RD in the R-CGC than ADHD-diagnosed methionine (met carriers, and val homozygote controls had higher FA and lower RD in the R-CGC than val homozygote ADHD patients. Second, met carriers had higher FA and axial diffusivity in the left (L-uncinate fasciculus and lower RD in the L-posterior corona radiata and L

  13. Catechol-O-methyltransferase Val158Met polymorphism influences prefrontal executive function in early Parkinson's disease.

    Science.gov (United States)

    Zhang, Youwen; Feng, Shujun; Nie, Kun; Zhao, Xin; Gan, Rong; Wang, Limin; Zhao, Jiehao; Tang, Hongmei; Gao, Liang; Zhu, Ruiming; Wang, Lijuan; Zhang, Yuhu

    2016-10-15

    The catechol-O-methyltransferase (COMT) Val158Met polymorphism has been proposed to be associated with increased risk of Parkinson's disease (PD) and have a specific impact on dopamine-mediated prefrontal executive function in an inverted-U curve manner. We explored the influence of this genetic polymorphism on prefrontal executive function in a well-established Chinese cohort of early PD patients with no current or past history of motor fluctuations or dyskinesias. Cognitive functions were assessed in 250 patients with early PD using Wechsler Adult Intelligence Scale-Chinese Revision (WAIS-RC) and Wechsler Memory Scale-Chinese Revision (WMS-RC). These patients and 300 healthy controls were subsequently genotyped for the COMT gene Val158Met polymorphism. We employed analysis of covariance (ANCOVA) and a stratified analysis to determine the associations between the COMT Val158Met genotype and cognitive functions. The COMT Val158Met allele frequency and genotype distributions showed no statistically significant differences between PD patients and controls. However, patients with met/met genotype performed significantly worse on WAIS-RC similarities, a measure of executive function, compared to individuals with val/val genotype. Subsequent ANCOVA analysis revealed that COMT genotype interacted with sex and daily levodopa equivalent dose (LED) to influence executive function. Further stratified analysis showed that the lower-activity COMT met/met genotype has a detrimental effect on executive function among women. Our results demonstrate that COMT Val158Met polymorphism is probably not associated with increased risk of PD, but has an effect on prefrontal executive function interacting with gender and dopaminergic medication. Copyright © 2016. Published by Elsevier B.V.

  14. Association of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety, ADHD and Tics in Children with Autism Spectrum Disorder

    Science.gov (United States)

    Gadow, Kenneth D.; Roohi, Jasmin; Devincent, Carla J.; Kirsch, Sarah; Hatchwell, Eli

    2009-01-01

    The aim of the study is to examine rs4680 ("COMT") and rs6265 ("BDNF") as genetic markers of anxiety, ADHD, and tics. Parents and teachers completed a DSM-IV-referenced rating scale for a total sample of 67 children with autism spectrum disorder (ASD). Both "COMT" (p = 0.06) and "BDNF" (p = 0.07) genotypes were marginally significant for teacher…

  15. Catechol-O-methyltransferase val158met polymorphism predicts placebo effect in irritable bowel syndrome.

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    Kathryn T Hall

    Full Text Available Identifying patients who are potential placebo responders has major implications for clinical practice and trial design. Catechol-O-methyltransferase (COMT, an important enzyme in dopamine catabolism plays a key role in processes associated with the placebo effect such as reward, pain, memory and learning. We hypothesized that the COMT functional val158met polymorphism, was a predictor of placebo effects and tested our hypothesis in a subset of 104 patients from a previously reported randomized controlled trial in irritable bowel syndrome (IBS. The three treatment arms from this study were: no-treatment ("waitlist", placebo treatment alone ("limited" and, placebo treatment "augmented" with a supportive patient-health care provider interaction. The primary outcome measure was change from baseline in IBS-Symptom Severity Scale (IBS-SSS after three weeks of treatment. In a regression model, the number of methionine alleles in COMT val158met was linearly related to placebo response as measured by changes in IBS-SSS (p = .035. The strongest placebo response occurred in met/met homozygotes treated in the augmented placebo arm. A smaller met/met associated effect was observed with limited placebo treatment and there was no effect in the waitlist control. These data support our hypothesis that the COMT val158met polymorphism is a potential biomarker of placebo response.

  16. Catechol-O-methyltransferase val158met polymorphism predicts placebo effect in irritable bowel syndrome.

    Science.gov (United States)

    Hall, Kathryn T; Lembo, Anthony J; Kirsch, Irving; Ziogas, Dimitrios C; Douaiher, Jeffrey; Jensen, Karin B; Conboy, Lisa A; Kelley, John M; Kokkotou, Efi; Kaptchuk, Ted J

    2012-01-01

    Identifying patients who are potential placebo responders has major implications for clinical practice and trial design. Catechol-O-methyltransferase (COMT), an important enzyme in dopamine catabolism plays a key role in processes associated with the placebo effect such as reward, pain, memory and learning. We hypothesized that the COMT functional val158met polymorphism, was a predictor of placebo effects and tested our hypothesis in a subset of 104 patients from a previously reported randomized controlled trial in irritable bowel syndrome (IBS). The three treatment arms from this study were: no-treatment ("waitlist"), placebo treatment alone ("limited") and, placebo treatment "augmented" with a supportive patient-health care provider interaction. The primary outcome measure was change from baseline in IBS-Symptom Severity Scale (IBS-SSS) after three weeks of treatment. In a regression model, the number of methionine alleles in COMT val158met was linearly related to placebo response as measured by changes in IBS-SSS (p = .035). The strongest placebo response occurred in met/met homozygotes treated in the augmented placebo arm. A smaller met/met associated effect was observed with limited placebo treatment and there was no effect in the waitlist control. These data support our hypothesis that the COMT val158met polymorphism is a potential biomarker of placebo response.

  17. Catechol-O-Methyltransferase val158met Polymorphism Predicts Placebo Effect in Irritable Bowel Syndrome

    Science.gov (United States)

    Hall, Kathryn T.; Lembo, Anthony J.; Kirsch, Irving; Ziogas, Dimitrios C.; Douaiher, Jeffrey; Jensen, Karin B.; Conboy, Lisa A.; Kelley, John M.; Kokkotou, Efi; Kaptchuk, Ted J.

    2012-01-01

    Identifying patients who are potential placebo responders has major implications for clinical practice and trial design. Catechol-O-methyltransferase (COMT), an important enzyme in dopamine catabolism plays a key role in processes associated with the placebo effect such as reward, pain, memory and learning. We hypothesized that the COMT functional val158met polymorphism, was a predictor of placebo effects and tested our hypothesis in a subset of 104 patients from a previously reported randomized controlled trial in irritable bowel syndrome (IBS). The three treatment arms from this study were: no-treatment (“waitlist”), placebo treatment alone (“limited”) and, placebo treatment “augmented” with a supportive patient-health care provider interaction. The primary outcome measure was change from baseline in IBS-Symptom Severity Scale (IBS-SSS) after three weeks of treatment. In a regression model, the number of methionine alleles in COMT val158met was linearly related to placebo response as measured by changes in IBS-SSS (p = .035). The strongest placebo response occurred in met/met homozygotes treated in the augmented placebo arm. A smaller met/met associated effect was observed with limited placebo treatment and there was no effect in the waitlist control. These data support our hypothesis that the COMT val158met polymorphism is a potential biomarker of placebo response. PMID:23110189

  18. The role of maternal stress during pregnancy, maternal discipline, and child COMT Val158Met genotype in the development of compliance.

    Science.gov (United States)

    Kok, Rianne; Bakermans-Kranenburg, Marian J; van Ijzendoorn, Marinus H; Velders, Fleur P; Linting, Mariëlle; Jaddoe, Vincent W V; Hofman, Albert; Verhulst, Frank C; Tiemeier, Henning

    2013-07-01

    Maternal discipline is an important predictor of child committed compliance. Maternal stress can affect both parenting and child development. In a large population-based cohort study (N = 613) we examined whether maternal discipline mediated the association between maternal stress during pregnancy and child compliance, and whether COMT or DRD4 polymorphisms moderated the association between maternal discipline and child compliance. Family-related and general stress were measured through maternal self-report and genetic material was collected through cord blood sampling at birth. Mother-child dyads were observed at 36 months in disciplinary tasks in which the child was not allowed to touch attractive toys. Maternal discipline and child compliance were observed in two different tasks and independently coded. The association between family stress during pregnancy and child committed compliance was mediated by maternal positive discipline. Children with more COMT Met alleles seemed more susceptible to maternal positive discipline than children with more COMT Val alleles.

  19. The Role of the Catechol-o-methyltransferase (COMT) Gene Val158Met in Aggressive Behavior, A Review of Genetic Studies

    Science.gov (United States)

    Qayyum, Arqam; Zai, Clement C.; Hirata, Yuko; Tiwari, Arun K.; Cheema, Sheraz; Nowrouzi, Behdin; Beitchman, Joseph H.; Kennedy, James L.

    2015-01-01

    Aggressive behaviors have become a major public health problem, and early-onset aggression can lead to outcomes such as substance abuse, antisocial personality disorder among other issues. In recent years, there has been an increase in research in the molecular and genetic underpinnings of aggressive behavior, and one of the candidate genes codes for the catechol-O-methyltransferase (COMT). COMT is involved in catabolizing catecholamines such as dopamine. These neurotransmitters appear to be involved in regulating mood which can contribute to aggression. The most common gene variant studied in the COMT gene is the Valine (Val) to Methionine (Met) substitution at codon 158. We will be reviewing the current literature on this gene variant in aggressive behavior. PMID:26630958

  20. Differences in 4-hydroxyestradiol levels in leukocytes are related to CYP1A1(∗)2C, CYP1B1(∗)3 and COMT Val158Met allelic variants.

    Science.gov (United States)

    Martínez-Ramírez, O C; Pérez-Morales, R; Petrosyan, P; Castro-Hernández, C; Gonsebatt, M E; Rubio, J

    2015-10-01

    Exposure to estrogen and its metabolites, including catechol estrogens (CEs) and catechol estrogen quinones (CE-Qs) is closely related to breast cancer. Polymorphisms of the genes involved in the catechol estrogens metabolism pathway (CEMP) have been shown to affect the production of CEs and CE-Qs. In this study, we measured the induction of CYP1A1, CYP1B1, COMT, and GSTP1 by 17β-estradiol (17β-E2) in leukocytes with CYP1A1(∗)2C, CYP1B1(∗)3, COMT Val158Met and GSTP1 Ile105Val polymorphisms by semi quantitative RT-PCR and compared the values to those of leukocytes with wild type alleles; we also compared the differences in formation of 4- hydroxyestradiol (4-OHE2) and DNA-adducts. The data show that in the leukocytes with mutant alleles treatment with 17β-E2 up-regulates CYP1A1 and CYP1B1 and down-regulates COMT mRNA levels, resulting in major increments in 4-OHE2 levels compared to leukocytes with wild-type alleles. Therefore, we propose induction levels of gene expression and intracellular 4-OHE2 concentrations associated with allelic variants in response to exposure of 17β-E2 as a noninvasive biomarker that can help determine the risk of developing non-hereditary breast cancer in women.

  1. Association between the catechol-o-methyltransferase val158met polymorphism with susceptibility and severity of carpal tunnel syndrome

    Directory of Open Access Journals (Sweden)

    Erkol İnal E

    2015-12-01

    Full Text Available Carpal tunnel syndrome (CTS is the most common entrapment neuropathy of the upper extremity. In this study, we aimed to clarify the relationships between the catechol-O-methyltransferase (COMT gene Val158Met (rs4680 polymorphism and development, functional and clinical status of CTS. Ninety-five women with electro diagnostically confirmed CTS and 95 healthy controls were enrolled in the study. The functional and clinical status of the patients was measured by the Turkish version of the Boston Questionnaire and intensity of pain related to the past 2 weeks was evaluated on a visual analog scale (VAS. The Val158Met polymorphism was determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP, method. We divided patients according to the genotypes of the Val158Met polymorphism as Val/Val, Val/Met and Met/Met. There were not any significant differences in terms of Val158Met polymorphisms between patients and healthy controls (p >0.05. We also did not find any relationships between the Val158Met polymorphism and CTS (p >0.05. In conclusion, although we did not find any relationships between CTS and the Val158Met polymorphism, we could not generalize this result to the general population. Future studies are warranted to conclude precise associations.

  2. Genetic contribution of catechol-O-methyltransferase polymorphism (Val158Met) in children with chronic tension-type headache.

    Science.gov (United States)

    Fernández-de-las-Peñas, César; Ambite-Quesada, Silvia; Rivas-Martínez, Inés; Ortega-Santiago, Ricardo; de-la-Llave-Rincón, Ana Isabel; Fernández-Mayoralas, Daniel M; Pareja, Juan A

    2011-10-01

    Our aim was to investigate the relationship between Val158Met polymorphisms, headache, and pressure hypersensitivity in children with chronic tension-type headache (CTTH). A case-control study with blinded assessor was conducted. Seventy children with CTTH associated with pericranial tenderness and 70 healthy children participated. After amplifying Val158Met polymorphism by polymerase chain reactions, we assessed genotype frequencies and allele distributions. We classified children according to their Val158Met polymorphism: Val/Val, Val/Met, Met/Met. Pressure pain thresholds (PPT) were bilaterally assessed over the temporalis, upper trapezius, second metacarpal, and tibialis anterior muscles. The distribution of Val158Met genotypes was not significantly different (p = 0.335), between children with CTTH and healthy children, and between boys and girls (p = 0.872). Children with CTTH with the Met/Met genotype showed a longer headache history compared with those with Met/Val (p = 0.001) or Val/Val (p = 0.002) genotype. Children with CTTH with Met/Met genotype showed lower PPT over upper trapezius and temporalis muscles than children with CTTH with Met/Val or Val/Val genotype (p < 0.01). The Val158Met catechol-O-methyltransferase (COMT) polymorphism does not appear to be involved in predisposition to suffer from CTTH in children; nevertheless, this genetic factor may be involved in the phenotypic expression, as pressure hypersensitivity was greater in those CTTH children with the Met/Met genotype.

  3. Gender-dependent association of the functional catechol-O-methyltransferase Val158Met genotype with sensation seeking personality trait.

    Science.gov (United States)

    Lang, Undine E; Bajbouj, Malek; Bajbouj, Malck; Sander, Thomas; Gallinat, Juergen

    2007-09-01

    The gene encoding cathechol-O-methyltransferase (COMT) contains a common functional missense polymorphism (Val158Met) that regulates dopamine in an allele-dependent manner. A pivotal role of dopamine neurotransmission in the prefrontal cortex has been implicated in drug-seeking behavior and related personality traits, such as sensation seeking, with some evidence for a gender-specific association. Here, we tested the hypothesis that the COMT Val158Met polymorphism modulates the personality dimension, sensation seeking, in a gender-dependent manner. Study sample included 214 male (age 38.1+/-12.6 years) and 218 female (age 36.1+/-13.6 years) healthy volunteers, who were assessed with Zuckerman's sensation-seeking scale and genotyped for the Val158Met polymorphism (dbSNP:rs4680). Univariate analysis of variance showed that the sensation seeking score was significantly affected by a COMT genotype x gender interaction (F=5.330, df=2, p=0.005). The Val158Met polymorphism was associated with the sensation seeking personality trait in women only. The highest scores in the sensation-seeking scale and in three of the four subscales were observed in female subjects with the Val/Val genotype relative to women carrying the Met allele. Our results suggest that high COMT enzyme activity associated with the Val allele predisposes to high sensation seeking scores in female subjects and add to increasing evidence for a gender specific role of COMT in normal and dysfunctional behavior.

  4. Association of Catechol-O-methyltransferase polymorphism Val158Met and mammographic density: A meta-analysis.

    Science.gov (United States)

    Kallionpää, Roope A; Uusitalo, Elina; Peltonen, Juha

    2017-08-15

    The Val158Met polymorphism in catechol-O-methyltransferase (COMT) enzyme reduces the methylation of catechol estrogens, which may affect mammographic density. High mammographic density is a known risk factor of breast cancer. Our aim was to perform meta-analysis of the effect of COMT Val158Met polymorphism on mammographic density. Original studies reporting data on mammographic density, stratified by the presence of COMT Val158Met polymorphism, were identified and combined using genetic models Met/Val vs. Val/Val, Met/Met vs. Val/Val, Val/Met+Met/Met vs. Val/Val (dominant model) and Met/Met vs. Val/Met+Val/Val (recessive model). Subgroup analyses by breast cancer status, menopausal status and use of hormone replacement therapy (HRT) were also performed. Eight studies were included in the meta-analysis. The overall effect in percent mammographic density was -1.41 (CI -2.86 to 0.05; P=0.06) in the recessive model. Exclusion of breast cancer patients increased the effect size to -1.93 (CI -3.49 to -0.37; P=0.02). The results suggested opposite effect of COMT Val158Met for postmenopausal users of HRT versus premenopausal women or postmenopausal non-users of HRT. COMT Val158Met polymorphism may be associated with mammographic density at least in healthy women. Menopausal status and HRT should be taken into account in future studies to avoid masking of the underlying effects. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Catechol-O-Methyltransferase Val158Met Polymorphism Is Associated with Somatosensory Amplification and Nocebo Responses

    Science.gov (United States)

    Benson, Sven; Engler, Harald; Engler, Andrea; Hinney, Anke; Rief, Winfried; Witzke, Oliver; Schedlowski, Manfred

    2014-01-01

    A large number of unwanted adverse events and symptoms reported by patients in clinical trials are not caused by the drug provided, since most of adverse events also occur in corresponding placebo groups. These nocebo effects also play a major role in drug discontinuation in clinical practice, negatively affecting treatment efficacy as well as patient adherence and compliance. Experimental and clinical data document a large interindividual variability in nocebo responses, however, data on psychological, biological or genetic predictors of nocebo responses are lacking. Thus, with an established paradigm of behaviorally conditioned immunosuppressive effects we analyzed possible genetic predictors for nocebo responses. We focused on the genetic polymorphisms in the catechol-O-methyltransferase (COMT) gene (Val158Met) and analyzed drug specific and general side effects before and after immunosuppressive medication and subsequent placebo intake in 62 healthy male subjects. Significantly more drug-specific as well as general side effects were reported from homozygous carriers of the Val158 variant during medication as well as placebo treatment compared to the other genotype groups. Val158/Val158 carriers also had significantly higher scores in the somatosensory amplification scale (SSAS) and the BMQ (beliefs about medicine questionnaire). Together these data demonstrate potential genetic and psychological variables predicting nocebo responses after drug and placebo intake, which might be utilized to minimize nocebo effects in clinical trials and medical practice. PMID:25222607

  6. Catechol-O-methyltransferase Val158Met polymorphism is associated with somatosensory amplification and nocebo responses.

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    Laura Wendt

    Full Text Available A large number of unwanted adverse events and symptoms reported by patients in clinical trials are not caused by the drug provided, since most of adverse events also occur in corresponding placebo groups. These nocebo effects also play a major role in drug discontinuation in clinical practice, negatively affecting treatment efficacy as well as patient adherence and compliance. Experimental and clinical data document a large interindividual variability in nocebo responses, however, data on psychological, biological or genetic predictors of nocebo responses are lacking. Thus, with an established paradigm of behaviorally conditioned immunosuppressive effects we analyzed possible genetic predictors for nocebo responses. We focused on the genetic polymorphisms in the catechol-O-methyltransferase (COMT gene (Val158Met and analyzed drug specific and general side effects before and after immunosuppressive medication and subsequent placebo intake in 62 healthy male subjects. Significantly more drug-specific as well as general side effects were reported from homozygous carriers of the Val158 variant during medication as well as placebo treatment compared to the other genotype groups. Val158/Val158 carriers also had significantly higher scores in the somatosensory amplification scale (SSAS and the BMQ (beliefs about medicine questionnaire. Together these data demonstrate potential genetic and psychological variables predicting nocebo responses after drug and placebo intake, which might be utilized to minimize nocebo effects in clinical trials and medical practice.

  7. Protective Role of Maternal P.VAL158MET Catechol-O-methyltransferase Polymorphism against Early-Onset Preeclampsia and its Complications

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    Krnjeta Tijana

    2016-09-01

    Full Text Available Background: Up until now there have been contradictory data about the association between p.Val158Met catechol-O-methyltransferase (COMT polymorphism and risk of preeclampsia (PE. The goal of this study was to assess the potential correlation between p.Val158Met COMT polymorphism and risk of early-onset PE, risk of a severe form of early-onset PE, as well as risk of small-for-gestationalage (SGA complicating PE.

  8. Cognitive control and the COMT Val158Met polymorphism: genetic modulation of videogame training and transfer to task-switching efficiency

    NARCIS (Netherlands)

    Colzato, L.S.; van den Wildenberg, W.P.M.; Hommel, B.

    2014-01-01

    The study investigated whether successful transfer of game-based cognitive improvements to untrained tasks might be modulated by preexisting neuro-developmental factors, such as genetic variability related to the catechol-O-methyltransferase (COMT)—an enzyme responsible for the degradation of dopami

  9. Predictors of heroin relapse: Personality traits, impulsivity, COMT gene Val158met polymorphism in a 5-year prospective study in Shanghai, China.

    Science.gov (United States)

    Su, Hang; Li, Zhibin; Du, Jiang; Jiang, Haifeng; Chen, Zhikang; Sun, Haiming; Zhao, Min

    2015-12-01

    Relapse is a typical feature of heroin addiction and rooted in genetic and psychological determinants. The aim of this study was to evaluate the effect of personality traits, impulsivity, and COMT gene polymorphism (rs4680) on relapse to heroin use during 5-year follow up. 564 heroin dependent patients were enrolled in compulsory drug rehabilitation center. 12 months prior to their release, personality traits were measured by BIS-11 (Barratt Impulsiveness Scale-11) and Temperament and Character Inventory (TCI). The COMT gene rs4680 polymorphism was genotyped using a DNA sequence detection system. The heroin use status was evaluated for 5 years after discharged. Among the 564 heroin-dependent patients, 500 were followed for 5 years after discharge and 53.0% (n = 265) were considered as relapsed to heroin use according to a strict monitor system. Univariate analysis showed that age, having ever been in methadone maintenance treatment (MMT), the total scores and non-planning scores of BIS-11, and the COMT rs4680 gene variants were different between relapse and abstinent groups. Logistic regression analysis showed higher BIS total score, having ever been in MMT and younger first heroin use age are the predictors of relapse to heroin use during 5 years follow-up, and the COMT rs4680 gene had an interaction with BIS scores. Our findings indicated that the impulsive personality traits, methadone use history, and onset age could predict relapse in heroin-dependent patients during 5 year's follow up. The COMT gene showed a moderational effect in part the relationship of impulsivity with heroin relapse.

  10. Catechol-O-methyltransferase Val158met Polymorphism Interacts With Early Experience to Predict Executive Functions in Early Childhood

    Science.gov (United States)

    Blair, Clancy; Sulik, Michael; Willoughby, Michael; Mills-Koonce, Roger; Petrill, Stephen; Bartlett, Christopher; Greenberg, Mark

    2017-01-01

    Numerous studies demonstrate that the Methionine variant of the catechol-O-methyltransferase Val158Met polymorphism, which confers less efficient catabolism of catecholamines, is associated with increased focal activation of prefrontal cortex (PFC) and higher levels of executive function abilities. By and large, however, studies of COMT Val158Met have been conducted with adult samples and do not account for the context in which development is occurring. Effects of early adversity on stress response physiology and the inverted U shape relating catecholamine levels to neural activity in PFC indicate the need to take into account early experience when considering relations between genes such as COMT and executive cognitive ability. Consistent with this neurobiology, we find in a prospective longitudinal sample of children and families (N=1292) that COMT Val158Met interacts with early experience to predict executive function abilities in early childhood. Specifically, the Valine variant of the COMT Val158Met polymorphism, which confers more rather than less efficient catabolism of catecholamines is associated with higher executive function abilities at child ages 48 and 60 months and with faster growth of executive function for children experiencing early adversity, as indexed by cumulative risk factors in the home at child ages 7, 15, 24, and 36 months. Findings indicate the importance of the early environment for the relation between catecholamine genes and developmental outcomes and demonstrate that the genetic moderation of environmental risk is detectable in early childhood. PMID:26251232

  11. Cathecol-O-methyl transferase Val158Met genotype is not a risk factor for conversion disorder.

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    Armagan, E; Almacıoglu, M L; Yakut, T; Köse, A; Karkucak, M; Köksal, O; Görükmez, O

    2013-03-19

    Alterations in catechol-O-methyltransferase (COMT) activity are involved in various types of neurological disorders. We examined a possible association between the COMT Val158Met polymorphism and conversion disorder in a study of 48 patients with conversion disorder and 48 control patients. In the conversion disorder group, 31 patients were Val/Met heterozygotes, 15 patients were Val/Val homozygotes and 2 patients were Met/Met homozygotes. In the control group, 32 patients were Val/Met heterozygotes and 16 patients were Val/Val homozygotes. There was no significant difference between the groups. We conclude that the COMT Val158Met genotype is quite common in Turkey and that it is not a risk factor for conversion disorder in the Turkish population.

  12. Study on the correlation between COMT gene Val158Met polymorphism and clinical efficacy of aripiprazole in the treatment of schizophrenic patients%儿茶酚胺氧位甲基转移酶基因 Val158Met 多态性与阿立哌唑治疗精神分裂症患者疗效的相关性研究

    Institute of Scientific and Technical Information of China (English)

    周鑫; 李康智; 秦群生

    2015-01-01

    Objective It is to approach the correlation of COMT gene Val 158Met polymorphism and clinical effect of aripi -prazole in treatment of schizophrenic patients .Methods 80 cases of schizophrenia patients received aripiprazole were selected as treatment group, 70 cases of healthy people who willing to volunteer spirit disease were selected as control group .The clini-cal data were retrospectively analyzed , as the treatment group.The genotyping were detected by Polymerase Chain Reaction re -striction fragment length polymorphism analysis (PCR -RFLP), the symptoms were evaluated by Positive and Negative Symp -tom Scale (PANSS).At the same time, the curative effects were observed.Results There was significant differences in the genotypes and allele frequency between both groups (all P 0.05).Conclusion COMT gene Val158Met polymorphism is not associated with the im -provement of clinical symptom , aripiprazole in treatment of schizophrenia patients to mental health , can effectively improve the patient's mental health and part of cognitive status .%目的:探讨儿茶酚胺氧位甲基转移酶(COMT)基因 Val158Met 多态性与阿立哌唑治疗精神分裂症患者疗效的相关性。方法选取接受阿立哌唑治疗的精神分裂症患者80例作为治疗组,选取同期愿意充当精神疾病志愿者的健康人70例作为对照组。应用即聚合酶链式反应-限制性片段长度多态分析(PCR -RFLP)与即阳性、阴性症状评定表(PAN-SS)进行基因分型与精神症状评定,同时观察应用阿立哌唑治疗的临床效果。结果2组的基因型及等位基因频率比较差异有统计学意义(P 均<0.05)。经阿立哌唑治疗后,患者PANSS 评分明显降低(P <0.05)。3种基因型应用阿立哌唑治疗后疗效比较差异无统计学意义(P 均>0.05)。结论COMT 基因 Val158Met 多态性并不关联于临床症状的改善,阿立哌唑治疗精神分裂,能够有效改善

  13. Catechol-O-methyltransferase val158met Polymorphism Interacts with Sex to Affect Face Recognition Ability

    Science.gov (United States)

    Lamb, Yvette N.; McKay, Nicole S.; Singh, Shrimal S.; Waldie, Karen E.; Kirk, Ian J.

    2016-01-01

    The catechol-O-methyltransferase (COMT) val158met polymorphism affects the breakdown of synaptic dopamine. Consequently, this polymorphism has been associated with a variety of neurophysiological and behavioral outcomes. Some of the effects have been found to be sex-specific and it appears estrogen may act to down-regulate the activity of the COMT enzyme. The dopaminergic system has been implicated in face recognition, a form of cognition for which a female advantage has typically been reported. This study aimed to investigate potential joint effects of sex and COMT genotype on face recognition. A sample of 142 university students was genotyped and assessed using the Faces I subtest of the Wechsler Memory Scale – Third Edition (WMS-III). A significant two-way interaction between sex and COMT genotype on face recognition performance was found. Of the male participants, COMT val homozygotes and heterozygotes had significantly lower scores than met homozygotes. Scores did not differ between genotypes for female participants. While male val homozygotes had significantly lower scores than female val homozygotes, no sex differences were observed in the heterozygotes and met homozygotes. This study contributes to the accumulating literature documenting sex-specific effects of the COMT polymorphism by demonstrating a COMT-sex interaction for face recognition, and is consistent with a role for dopamine in face recognition. PMID:27445927

  14. Catechol-O-methyltransferase val(158)met Polymorphism Interacts with Sex to Affect Face Recognition Ability.

    Science.gov (United States)

    Lamb, Yvette N; McKay, Nicole S; Singh, Shrimal S; Waldie, Karen E; Kirk, Ian J

    2016-01-01

    The catechol-O-methyltransferase (COMT) val158met polymorphism affects the breakdown of synaptic dopamine. Consequently, this polymorphism has been associated with a variety of neurophysiological and behavioral outcomes. Some of the effects have been found to be sex-specific and it appears estrogen may act to down-regulate the activity of the COMT enzyme. The dopaminergic system has been implicated in face recognition, a form of cognition for which a female advantage has typically been reported. This study aimed to investigate potential joint effects of sex and COMT genotype on face recognition. A sample of 142 university students was genotyped and assessed using the Faces I subtest of the Wechsler Memory Scale - Third Edition (WMS-III). A significant two-way interaction between sex and COMT genotype on face recognition performance was found. Of the male participants, COMT val homozygotes and heterozygotes had significantly lower scores than met homozygotes. Scores did not differ between genotypes for female participants. While male val homozygotes had significantly lower scores than female val homozygotes, no sex differences were observed in the heterozygotes and met homozygotes. This study contributes to the accumulating literature documenting sex-specific effects of the COMT polymorphism by demonstrating a COMT-sex interaction for face recognition, and is consistent with a role for dopamine in face recognition.

  15. Catechol-O-methyltransferase Val158Met polymorphism associates with individual differences in sleep physiologic responses to chronic sleep loss.

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    Namni Goel

    Full Text Available BACKGROUND: The COMT Val158Met polymorphism modulates cortical dopaminergic catabolism, and predicts individual differences in prefrontal executive functioning in healthy adults and schizophrenic patients, and associates with EEG differences during sleep loss. We assessed whether the COMT Val158Met polymorphism was a novel marker in healthy adults of differential vulnerability to chronic partial sleep deprivation (PSD, a condition distinct from total sleep loss and one experienced by millions on a daily and persistent basis. METHODOLOGY/PRINCIPAL FINDINGS: 20 Met/Met, 64 Val/Met, and 45 Val/Val subjects participated in a protocol of two baseline 10h time in bed (TIB nights followed by five consecutive 4 h TIB nights. Met/Met subjects showed differentially steeper declines in non-REM EEG slow-wave energy (SWE-the putative homeostatic marker of sleep drive-during PSD, despite comparable baseline SWE declines. Val/Val subjects showed differentially smaller increases in slow-wave sleep and smaller reductions in stage 2 sleep during PSD, and had more stage 1 sleep across nights and a shorter baseline REM sleep latency. The genotypes, however, did not differ in performance across various executive function and cognitive tasks and showed comparable increases in subjective and physiological sleepiness in response to chronic sleep loss. Met/Met genotypic and Met allelic frequencies were higher in whites than African Americans. CONCLUSIONS/SIGNIFICANCE: The COMT Val158Met polymorphism may be a genetic biomarker for predicting individual differences in sleep physiology-but not in cognitive and executive functioning-resulting from sleep loss in a healthy, racially-diverse adult population of men and women. Beyond healthy sleepers, our results may also provide insight for predicting sleep loss responses in patients with schizophrenia and other psychiatric disorders, since these groups repeatedly experience chronically-curtailed sleep and demonstrate COMT

  16. Affect-modulated startle: interactive influence of catechol-O-methyltransferase Val158Met genotype and childhood trauma.

    Science.gov (United States)

    Klauke, Benedikt; Winter, Bernward; Gajewska, Agnes; Zwanzger, Peter; Reif, Andreas; Herrmann, Martin J; Dlugos, Andrea; Warrings, Bodo; Jacob, Christian; Mühlberger, Andreas; Arolt, Volker; Pauli, Paul; Deckert, Jürgen; Domschke, Katharina

    2012-01-01

    The etiology of emotion-related disorders such as anxiety or affective disorders is considered to be complex with an interaction of biological and environmental factors. Particular evidence has accumulated for alterations in the dopaminergic and noradrenergic system--partly conferred by catechol-O-methyltransferase (COMT) gene variation--for the adenosinergic system as well as for early life trauma to constitute risk factors for those conditions. Applying a multi-level approach, in a sample of 95 healthy adults, we investigated effects of the functional COMT Val158Met polymorphism, caffeine as an adenosine A2A receptor antagonist (300 mg in a placebo-controlled intervention design) and childhood maltreatment (CTQ) as well as their interaction on the affect-modulated startle response as a neurobiologically founded defensive reflex potentially related to fear- and distress-related disorders. COMT val/val genotype significantly increased startle magnitude in response to unpleasant stimuli, while met/met homozygotes showed a blunted startle response to aversive pictures. Furthermore, significant gene-environment interaction of COMT Val158Met genotype with CTQ was discerned with more maltreatment being associated with higher startle potentiation in val/val subjects but not in met carriers. No main effect of or interaction effects with caffeine were observed. Results indicate a main as well as a GxE effect of the COMT Val158Met variant and childhood maltreatment on the affect-modulated startle reflex, supporting a complex pathogenetic model of the affect-modulated startle reflex as a basic neurobiological defensive reflex potentially related to anxiety and affective disorders.

  17. Affect-modulated startle: interactive influence of catechol-O-methyltransferase Val158Met genotype and childhood trauma.

    Directory of Open Access Journals (Sweden)

    Benedikt Klauke

    Full Text Available The etiology of emotion-related disorders such as anxiety or affective disorders is considered to be complex with an interaction of biological and environmental factors. Particular evidence has accumulated for alterations in the dopaminergic and noradrenergic system--partly conferred by catechol-O-methyltransferase (COMT gene variation--for the adenosinergic system as well as for early life trauma to constitute risk factors for those conditions. Applying a multi-level approach, in a sample of 95 healthy adults, we investigated effects of the functional COMT Val158Met polymorphism, caffeine as an adenosine A2A receptor antagonist (300 mg in a placebo-controlled intervention design and childhood maltreatment (CTQ as well as their interaction on the affect-modulated startle response as a neurobiologically founded defensive reflex potentially related to fear- and distress-related disorders. COMT val/val genotype significantly increased startle magnitude in response to unpleasant stimuli, while met/met homozygotes showed a blunted startle response to aversive pictures. Furthermore, significant gene-environment interaction of COMT Val158Met genotype with CTQ was discerned with more maltreatment being associated with higher startle potentiation in val/val subjects but not in met carriers. No main effect of or interaction effects with caffeine were observed. Results indicate a main as well as a GxE effect of the COMT Val158Met variant and childhood maltreatment on the affect-modulated startle reflex, supporting a complex pathogenetic model of the affect-modulated startle reflex as a basic neurobiological defensive reflex potentially related to anxiety and affective disorders.

  18. No association between chronic musculoskeletal complaints and Val158Met polymorphism in the Catechol-O-methyltransferase gene. The HUNT study

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    Stovner Lars

    2006-05-01

    Full Text Available Abstract Background The Catechol-O-methyltransferase (COMT gene contains a functional polymorphism, Val158Met, that has been found to influence human pain perception. In one study fibromyalgia was less likely among those with Val/Val genotype. Methods In the 1995–97 Nord-Trøndelag Health Study (HUNT, the association between Val/Met polymorphism at the COMT gene and chronic musculoskeletal complaints (MSCs was evaluated in a random sample of 3017 individuals. Results The distribution of the COMT Val158Met genotypes and alleles were similar between controls and the twelve different chronic MSCs groups. Even when the Met/Met and Val/Met genotypes were pooled, the distribution of the Val/Val genotype and other genotypes were similar between controls and the chronic MSCs groups. Conclusion In this population-based study, no significant association was found between Val/Met polymorphism at the COMT gene and chronic MSCs.

  19. The influence of the Val158Met catechol-O-methyltransferase polymorphism on the personality traits of bipolar patients.

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    Wendy Dávila

    Full Text Available INTRODUCTION: Certain personality traits and genetic polymorphisms are contributing factors to bipolar disorder and its symptomatology, and in turn, this syndrome influences personality. The aim of the present study is to compare the personality traits of euthymic bipolar patients with healthy controls and to investigate the effect of the catechol-O-methyltransferase (COMT Val158Met genotype on those traits. We recruited thirty seven bipolar I patients in euthymic state following a manic episode and thirty healthy controls and evaluated their personality by means of the Cloninger's Temperament and Character Inventory (version TCI-R-140. We assessed the influence of the polymorphism Val158Met in the COMT gene on the personality of these patients. The patients scored higher than controls in harm avoidance (61.3±12.5 vs. 55.3±8.1 and self-transcendence (45.3±12.8 vs. 32.7±8.2 and scored lower than controls in self-directedness (68.8±13.3 vs. 79.3±8.1, cooperativeness (77.1±9.1 vs. 83.9±6.5 and persistence (60.4±15.1 vs. 67.1±8.9. The novelty seeking dimension associates with the Val158Met COMT genotype; patients with the low catabolic activity genotype, Met/Met, show a higher score than those with the high catabolic activity genotype, Val/Val. CONCLUSIONS: Suffering from bipolar disorder could have an impact on personality. A greater value in harm avoidance may be a genetic marker for a vulnerability to the development of a psychiatric disorder, but not bipolar disorder particularly, while a low value in persistence may characterize affective disorders or a subgroup of bipolar patients. The association between novelty seeking scores and COMT genotype may be linked with the role dopamine plays in the brain's reward circuits.

  20. The effects of catechol-O-methyl-transferase polymorphism Val158Met on functional connectivity in healthy young females: a resting EEG study.

    Science.gov (United States)

    Lee, Tien-Wen; Yu, Younger W-Y; Hong, Chen-Jee; Tsai, Shih-Jen; Wu, Hung-Chi; Chen, Tai-Jui

    2011-03-04

    The catechol-O-methyl-transferase (COMT) gene has been linked to a wide spectrum of human phenotypes, including cognition, affective response, pain sensitivity, anxiety and psychosis. This study examined the modulatory effects of COMT Val158Met on neural interactions, indicated by connectivity strengths. Blood samples and resting state eyes-closed EEG signals were collected in 254 healthy young females. The COMT Val158Met polymorphism was decoded into 3 groups: Val/Val, Val/Met and Met/Met. The values of mutual information of 20 frontal-related channel pairs across delta, theta, alpha and beta frequencies were analyzed based on the time-frequency mutual information method. Our one-way ANOVA analyses revealed that the significant connection-frequency pairs were relatively left lateralized (PF7-T3 and F7-C3 at delta frequency, and F3-F4, F7-T3, F7-C3, F7-P3, F3-C3, F3-F7 and F4-F8 at theta frequency. The F-test at F7-T3 and F7-C3 theta surpassed the statistical threshold of PVal/Met>Met/Met. Our analyses complemented previous literature regarding neural modulation by the COMT Val158Met polymorphism. The implication to the pathogenesis in schizophrenia was also discussed. Further studies are needed to clarify whether there is gender difference on this gene-brain interaction. Copyright © 2010 Elsevier B.V. All rights reserved.

  1. Catechol-O-methyltransferase val158met genotype determines effect of reboxetine on emotional memory in healthy male volunteers

    Science.gov (United States)

    Gibbs, Ayana A.; Bautista, Carla E.; Mowlem, Florence D.; Naudts, Kris H.; Duka, Dora T.

    2014-01-01

    Background Catechol-O-methyltransferase (COMT) metabolizes catecholamines in the prefrontal cortex (PFC). A common polymorphism in the COMT gene (COMT val158met) has pleiotropic effects on cognitive and emotional processing. The met allele has been associated with enhanced cognitive processing but impaired emotional processing relative to the val allele. Methods We genotyped healthy, white men in relation to the COMT val158met polymorphism. They were given a single 4 mg dose of the selective noradrenaline reuptake inhibitor (NRI) reboxetine or placebo in a randomized, double-blind between-subjects model and then completed an emotional memory task 2 hours later. Results We included 75 men in the study; 41 received reboxetine and 34 received placebo. In the placebo group, met/met carriers did not demonstrate the usual memory advantage for emotional stimuli that was observed in val carriers. Reboxetine restored this emotional enhancement of memory in met/met carriers, but had no significant effect in val carriers. Limitations We studied only men, thus limiting the generalizability of our findings. We also relied on self-reported responses to screening questions to establish healthy volunteer status, and in spite of the double-blind design, participants were significantly better than chance at identifying their intervention allocation. Conclusion Emotional memory is impaired in healthy met homozygotes and selectively improved in this group by reboxetine. This has potential translational implications for the use of reboxetine, which is currently licensed as an antidepressant in several countries, and edivoxetine, a new selective NRI currently in development. PMID:24467942

  2. The catechol-o-methyltransferase Val158Met polymorphism modulates the intrinsic functional network centrality of the parahippocampal cortex in healthy subjects

    Science.gov (United States)

    Zhang, Xiaolong; Li, Jin; Qin, Wen; Yu, Chunshui; Liu, Bing; Jiang, Tianzi

    2015-01-01

    The influence of catechol-o-methyltransferase (COMT) Val158Met on brain activation and functional connectivity has been widely reported. However, voxel-wise effects of this genotype on resting-state brain networks remain unclear. Here, we used resting-state fMRI and eigenvector centrality to examine the effects of COMT Val158Met genotypes on the connection patterns of the brain network and working memory (WM) in healthy, young Val/Val and Met carrier subjects. There were significant differences in the performance level on the 2-back WM task between the different COMT genotypes: Val/Val individuals exhibited a higher correct rate compared to the Met carriers. A two-sample t test was used to examine the differences in the eigenvector centrality maps, using age and gender as covariates of no interest, between the Val/Val and Met carriers. We found that the Val/Val individuals exhibited significantly higher eigenvector centrality compared to the Met carriers in the left parahippocampal cortex. Furthermore, a significantly positive correlation between the mean eigenvector centrality of the significant cluster and the correct rate of the 2-back WM task was observed. By using a voxel-wise data-driven method, our findings may provide plausible implications regarding individual differences in the genetic contribution of COMT Val158Met to the brain network and cognition. PMID:26054510

  3. The Role of a Catechol-O-Methyltransferase (COMT) Val158Met Genetic Polymorphism in Schizophrenia: A Systematic Review and Updated Meta-analysis on 32,816 Subjects.

    Science.gov (United States)

    González-Castro, Thelma Beatriz; Hernández-Díaz, Yazmin; Juárez-Rojop, Isela Esther; López-Narváez, María Lilia; Tovilla-Zárate, Carlos Alfonso; Fresan, Ana

    2016-06-01

    An association between a catechol-O-methyltransferase (COMT) Val156Met (rs4680) polymorphism and schizophrenia has been reported in the literature, although no conclusive outcomes have been attained. The aim of this study was to evaluate the association of the COMT Val108/158Met polymorphism with schizophrenia in a systematic review and meta-analysis. We performed a keyword search on PubMed and EBSCO databases. All English language case-control studies published up to April 2015 were selected. A total of 67 studies were selected for inclusion. The genotype distribution of subjects with schizophrenia was compared with healthy control subjects, using allelic, additive, dominant and recessive models. The pooled results from the meta-analysis (15,565 cases and 17,251 healthy subjects) after the elimination of heterogeneity showed an association between COMT Val108/158Met and schizophrenia [recessive model: OR 1.08 CI 95 % (1.01-1.15)]. We conducted subgroup analyses according to ethnicity. An association was observed in our Caucasian population in the additive model [OR 1.21 CI 95 % (1.06-1.37)] and in the recessive model [OR 1.21 CI 95 % (1.11-1.32)], but not in the allelic or dominant models. However, when we analysed our Asian population after the elimination of heterogeneity, no evidence of a significant association was found in any of the genetic models. Our analyses indicate that there is an association between COMT Val108/158Met and schizophrenia in the general population. Furthermore, in Caucasian populations, this risk could be increased.

  4. Differential Effects of the Catechol-O-Methyltransferase Val158Met Genotype on the Cognitive Function of Schizophrenia Patients and Healthy Japanese Individuals

    Science.gov (United States)

    Tsuchimine, Shoko; Yasui-Furukori, Norio; Kaneda, Ayako; Kaneko, Sunao

    2013-01-01

    Background The functional polymorphism Val158Met in the catechol-O-methyltransferase (COMT) gene has been associated with differences in prefrontal cognitive functions in patients with schizophrenia and healthy individuals. Several studies have indicated that the Met allele is associated with better performance on measures of cognitive function. We investigated whether the COMT Val158Met genotype was associated with cognitive function in 149 healthy controls and 118 patients with schizophrenia. Methods Cognitive function, including verbal memory, working memory, motor speed, attention, executive function and verbal fluency, was assessed by the Brief Assessment of Cognition in Schizophrenia (BACS-J). We employed a one-way analysis of variance (ANOVA) and a multiple regression analysis to determine the associations between the COMT Val158Met genotype and the BACS-J measurements. Results The one-way ANOVA revealed a significant difference in the scores on the Tower of London, a measure of executive function, between the different Val158Met genotypes in the healthy controls (p = 0.023), and a post-hoc analysis showed significant differences between the scores on the Tower of London in the val/val genotype group (18.6 ± 2.4) compared to the other two groups (17.6 ± 2.7 for val/met and 17.1 ± 3.2 for met/met; p = 0.027 and p = 0.024, respectively). Multiple regression analyses revealed that executive function was significantly correlated with the Val158Met genotype (p = 0.003). However, no evidence was found for an effect of the COMT on any cognitive domains of the BACS-J in the patients with schizophrenia. Conclusion These data support the hypothesis that the COMT Val158Met genotype maintains an optimal level of dopamine activity. Further studies should be performed that include a larger sample size and include patients on and off medication, as these patients would help to confirm our findings. PMID:24282499

  5. Differential effects of the catechol-O-methyltransferase Val158Met genotype on the cognitive function of schizophrenia patients and healthy Japanese individuals.

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    Shoko Tsuchimine

    Full Text Available BACKGROUND: The functional polymorphism Val158Met in the catechol-O-methyltransferase (COMT gene has been associated with differences in prefrontal cognitive functions in patients with schizophrenia and healthy individuals. Several studies have indicated that the Met allele is associated with better performance on measures of cognitive function. We investigated whether the COMT Val158Met genotype was associated with cognitive function in 149 healthy controls and 118 patients with schizophrenia. METHODS: Cognitive function, including verbal memory, working memory, motor speed, attention, executive function and verbal fluency, was assessed by the Brief Assessment of Cognition in Schizophrenia (BACS-J. We employed a one-way analysis of variance (ANOVA and a multiple regression analysis to determine the associations between the COMT Val158Met genotype and the BACS-J measurements. RESULTS: The one-way ANOVA revealed a significant difference in the scores on the Tower of London, a measure of executive function, between the different Val158Met genotypes in the healthy controls (p = 0.023, and a post-hoc analysis showed significant differences between the scores on the Tower of London in the val/val genotype group (18.6 ± 2.4 compared to the other two groups (17.6 ± 2.7 for val/met and 17.1 ± 3.2 for met/met; p = 0.027 and p = 0.024, respectively. Multiple regression analyses revealed that executive function was significantly correlated with the Val158Met genotype (p = 0.003. However, no evidence was found for an effect of the COMT on any cognitive domains of the BACS-J in the patients with schizophrenia. CONCLUSION: These data support the hypothesis that the COMT Val158Met genotype maintains an optimal level of dopamine activity. Further studies should be performed that include a larger sample size and include patients on and off medication, as these patients would help to confirm our findings.

  6. The Influence of the Val158Met Catechol-O-Methyltransferase Polymorphism on the Personality Traits of Bipolar Patients

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    Dávila, Wendy; Basterreche, Nieves; Arrue, Aurora; Zamalloa, María I.; Gordo, Estíbaliz; Dávila, Ricardo; González-Torres, Miguel A.; Zumárraga, Mercedes

    2013-01-01

    Introduction Certain personality traits and genetic polymorphisms are contributing factors to bipolar disorder and its symptomatology, and in turn, this syndrome influences personality. The aim of the present study is to compare the personality traits of euthymic bipolar patients with healthy controls and to investigate the effect of the catechol-O-methyltransferase (COMT) Val158Met genotype on those traits. We recruited thirty seven bipolar I patients in euthymic state following a manic episode and thirty healthy controls and evaluated their personality by means of the Cloninger’s Temperament and Character Inventory (version TCI-R-140). We assessed the influence of the polymorphism Val158Met in the COMT gene on the personality of these patients. The patients scored higher than controls in harm avoidance (61.3±12.5 vs. 55.3±8.1) and self-transcendence (45.3±12.8 vs. 32.7±8.2) and scored lower than controls in self-directedness (68.8±13.3 vs. 79.3±8.1), cooperativeness (77.1±9.1 vs. 83.9±6.5) and persistence (60.4±15.1 vs. 67.1±8.9). The novelty seeking dimension associates with the Val158Met COMT genotype; patients with the low catabolic activity genotype, Met/Met, show a higher score than those with the high catabolic activity genotype, Val/Val. Conclusions Suffering from bipolar disorder could have an impact on personality. A greater value in harm avoidance may be a genetic marker for a vulnerability to the development of a psychiatric disorder, but not bipolar disorder particularly, while a low value in persistence may characterize affective disorders or a subgroup of bipolar patients. The association between novelty seeking scores and COMT genotype may be linked with the role dopamine plays in the brain’s reward circuits. PMID:23646156

  7. Catechol-O-methyltransferase Val158Met polymorphism modulates gray matter volume and functional connectivity of the default mode network.

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    Tian Tian

    Full Text Available The effect of catechol-O-methyltransferase (COMT Val158Met polymorphism on brain structure and function has been previously investigated separately and regionally; this prevents us from obtaining a full picture of the effect of this gene variant. Additionally, gender difference must not be overlooked because estrogen exerts an interfering effect on COMT activity. We examined 323 young healthy Chinese Han subjects and analyzed the gray matter volume (GMV differences between Val/Val individuals and Met carriers in a voxel-wise manner throughout the whole brain. We were interested in genotype effects and genotype × gender interactions. We then extracted these brain regions with GMV differences as seeds to compute resting-state functional connectivity (rsFC with the rest of the brain; we also tested the genotypic differences and gender interactions in the rsFCs. Val/Val individuals showed decreased GMV in the posterior cingulate cortex (PCC compared with Met carriers; decreased GMV in the medial superior frontal gyrus (mSFG was found only in male Val/Val subjects. The rsFC analysis revealed that both the PCC and mSFG were functionally correlated with brain regions of the default mode network (DMN. Both of these regions showed decreased rsFCs with different parts of the frontopolar cortex of the DMN in Val/Val individuals than Met carriers. Our findings suggest that the COMT Val158Met polymorphism modulates both the structure and functional connectivity within the DMN and that gender interactions should be considered in studies of the effect of this genetic variant, especially those involving prefrontal morphology.

  8. The impact of the Catechol-O-methyltransferase Val158Met polymorphism on survival in the general population – the HUNT study

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    Skorpen Frank

    2007-06-01

    Full Text Available Abstract Background The catechol-O-methyltransferase (COMT gene contains a functional polymorphism, Val158Met which has been related to common diseases like cancer, psychiatric illness and myocardial infarction. Whether the Val158Met polymorphism is associated with survival has not been evaluated in the general population. The aim of this prospective study was to evaluate the impact of codon 158 COMT gene polymorphism on survival in a population-based cohort. Methods The sample comprised 2979 non-diabetic individuals who participated in the Nord-Trøndelag Health Study (HUNT in the period 1995–97. The subjects were followed up with respect to mortality throughout year 2004. Results 212 men and 183 women died during the follow up. No association between codon 158 COMT gene polymorphism and survival was found. The unadjusted relative risk of death by non-ischemic heart diseases with Met/Met or Met/Val genotypes was 3.27 (95% confidence interval, 1.19–9.00 compared to Val/Val genotype. When we adjusted for age, gender, smoking, coffee intake and body mass index the relative risk decreased to 2.89 (95% confidence interval, 1.04–8.00. Conclusion During 10 year of follow-up, the Val158Met polymorphism had no impact on survival in a general population. Difference in mortality rates from non-ischemic heart diseases may be incidental and should be evaluated in other studies.

  9. Depression and anxiety in relation to catechol-O-methyltransferase Val158Met genotype in the general population: The Nord-Trøndelag Health Study (HUNT

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    Zwart John-Anker

    2008-06-01

    Full Text Available Abstract Background The catechol-O-methyltransferase (COMT gene contains a functional polymorphism, Val158Met, which has been linked to anxiety and depression, but previous results are not conclusive. The aim of the present study was to examine the relationship between the Val158Met COMT gene polymorphism and anxiety and depression measured by the Hospital Anxiety and Depression Scale (HADS in the general adult population. Methods In the Nord-Trøndelag Health Study (HUNT the association between the Val158Met polymorphism and anxiety and depression was evaluated in a random sample of 5531 individuals. Two different cut off scores (≥ 8 and ≥ 11 were used to identify cases with anxiety (HADS-A and depression (HADS-D, whereas controls had HADS-A Results The COMT genotype distribution was similar between controls and individuals in the groups with anxiety and depression using cut-off scores of ≥ 8. When utilizing the alternative cut-off score HADS-D ≥ 11, Met/Met genotype and Met allele were less common among men with depression compared to the controls (genotype: p = 0.017, allele: p = 0.006. In the multivariate analysis, adjusting for age and heart disease, depression (HADS-D ≥ 11 was less likely among men with the Met/Met genotype than among men with the Val/Val genotype (OR = 0.37, 95% CI = 0.18–0.76. Conclusion In this population-based study, no clear association between the Val158Met polymorphism and depression and anxiety was revealed. The Met/Met genotype was less likely among men with depression defined as HADS-D ≥ 11, but this may be an incidental finding.

  10. Association of the Catechol O-Methyltransferase Val158-Met Polymorphism and Reduced Interference Control in Korean Children with Attention-Deficit Hyperactivity Disorder

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    Park, Subin; Park, Jong-Eun; Yoo, Hee Jeong; Kim, Jae-Won; Cheong, Jae Hoon; Han, Doug Hyun; Kim, Yeni

    2015-01-01

    Objective We tested for association of the catechol-O-methyltransferase (COMT) Val158-Met (rs4680) polymorphism with attention-deficit hyperactivity disorder (ADHD) using family-based test in Korean trios. Methods A total of 181 subjects with ADHD along with both of their biological parents were recruited from University Hospitals in Korea. We performed a transmission disequilibrium test (TDT) on 181 trios. Results In the TDT, we found the over-transmission of the Val allele in children with ADHD (χ2=4.21, p=0.040). Conclusion These results suggest that the COMT Val158-Met polymorphism is associated with ADHD among the Korean population. However, this study must be replicated in larger populations. PMID:26508970

  11. Catechol-O-methyltransferase Val158Met polymorphism on the relationship between white matter hyperintensity and cognition in healthy people.

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    Mu-En Liu

    Full Text Available BACKGROUND: White matter lesions can be easily observed on T2-weighted MR images, and are termed white matter hyperintensities (WMH. Their presence may be correlated with cognitive impairment; however, the relationship between regional WMH volume and catechol-O-methyltransferase (COMT Val158Met polymorphism in healthy populations remains unclear. METHODS: We recruited 315 ethnic Chinese adults with a mean age of 54.9 ± 21.8 years (range: 21-89 y to examine the genetic effect of COMT on regional WMH and the manner in which they interact to affect cognitive function in a healthy adult population. Cognitive tests, structural MRI scans, and genotyping of COMT were conducted for each participant. RESULTS: Negative correlations between the Digit Span Forward (DSF score and frontal WMH volumes (r = -.123, P = .032, uncorrected were noted. For the genetic effect of COMT, no significant difference in cognitive performance was observed among 3 genotypic groups. However, differences in WMH volumes over the subcortical region (P = .016, uncorrected, whole brain (P = .047, uncorrected, and a trend over the frontal region (P = .050, uncorrected were observed among 3 COMT genotypic groups. Met homozygotes and Met/Val heterozygotes exhibited larger WMH volumes in these brain regions than the Val homozygotes. Furthermore, a correlation between the DSF and regional WMH volume was observed only in Met homozygotes. The effect size (cohen's f revealed a small effect. CONCLUSIONS: The results indicate that COMT might modulate WMH volumes and the effects of WMH on cognition.

  12. Catechol-O-Methyltransferase Val158Met Polymorphism on the Relationship between White Matter Hyperintensity and Cognition in Healthy People

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    Liu, Mu-En; Huang, Chu-Chung; Yang, Albert C.; Tu, Pei-Chi; Yeh, Heng-Liang; Hong, Chen-Jee; Liou, Ying-Jay; Chen, Jin-Fan; Chou, Kun-Hsien; Lin, Ching-Po; Tsai, Shih-Jen

    2014-01-01

    Background White matter lesions can be easily observed on T2-weighted MR images, and are termed white matter hyperintensities (WMH). Their presence may be correlated with cognitive impairment; however, the relationship between regional WMH volume and catechol-O-methyltransferase (COMT) Val158Met polymorphism in healthy populations remains unclear. Methods We recruited 315 ethnic Chinese adults with a mean age of 54.9±21.8 years (range: 21–89 y) to examine the genetic effect of COMT on regional WMH and the manner in which they interact to affect cognitive function in a healthy adult population. Cognitive tests, structural MRI scans, and genotyping of COMT were conducted for each participant. Results Negative correlations between the Digit Span Forward (DSF) score and frontal WMH volumes (r = −.123, P = .032, uncorrected) were noted. For the genetic effect of COMT, no significant difference in cognitive performance was observed among 3 genotypic groups. However, differences in WMH volumes over the subcortical region (P = .016, uncorrected), whole brain (P = .047, uncorrected), and a trend over the frontal region (P = .050, uncorrected) were observed among 3 COMT genotypic groups. Met homozygotes and Met/Val heterozygotes exhibited larger WMH volumes in these brain regions than the Val homozygotes. Furthermore, a correlation between the DSF and regional WMH volume was observed only in Met homozygotes. The effect size (cohen’s f) revealed a small effect. Conclusions The results indicate that COMT might modulate WMH volumes and the effects of WMH on cognition. PMID:24551149

  13. The Catechol-O-Methyltransferase Val158Met Polymorphism Contributes to the Risk of Breast Cancer in the Chinese Population: An Updated Meta-Analysis

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    Wan, Guo-Xing; Cao, Yu-Wen; Li, Wen-Qin; Li, Yu-Cong; Li, Feng

    2014-01-01

    Purpose Catechol-O-methyltransferase (COMT) enzyme plays a central role in estrogen-induced carcinogenesis. Emerging evidence from association studies has revealed that the functional Val158Met polymorphism (rs4680 G>A) of the Catechol-O-methyltransferase gene (COMT) has been implicated in susceptibility to breast cancer in the Chinese population, while results of individual published studies remain inconclusive and inconsistent. To assess this association in the Chinese population, a meta-analysis was performed. Methods Eligible studies were searched on MEDLINE, Embase, Cochrane Library, China National Knowledge Infrastructure, and the Chinese Biomedicine Database. Odds ratios (ORs) with their corresponding 95% confidence intervals (CIs) were pooled to assess the association between COMT polymorphisms and the risk of breast cancer using RevMan 5.2 and Stata 12.0 software. Results The meta-analysis included 14 eligible studies, with a total of 4,626 breast cancer cases and 5,637 controls. Overall, the COMT Val158Met polymorphism (rs4680 G>A) was significantly associated with an increased risk of breast cancer in several genetic models (A/A vs. G/G: OR, 1.59, 95% CI, 1.12-2.27; A/A vs. G/A+G/G: OR, 1.62, 95% CI, 1.14-2.29; A vs. G: OR, 1.15, 95% CI, 1.00-1.32), and a subgroup analysis according to menopausal status showed that this association was especially evident among premenopausal Chinese women (A/A vs. G/G: OR, 1.87, 95% CI, 0.99-3.54; A/A vs. G/A+G/G: OR, 1.94, 95% CI, 1.03-3.63). Conclusion The results of this meta-analysis indicated that COMT Val158Met variants contribute to breast cancer susceptibility in the Chinese population, particularly among premenopausal women. PMID:25013436

  14. Dopamine D3 Receptor Ser9Gly and Catechol-O-methyltransferase Val158Met Polymorphisms and Acute Pain in Sickle Cell Disease

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    Jhun, Ellie; He, Ying; Yao, Yingwei; Molokie, Robert E.; Wilkie, Diana J.; Wang, Zaijie Jim

    2014-01-01

    Background Pain in sickle cell disease (SCD) is characterized by episodes of acute pain, primarily responsible for acute health care utilization, and persistent chronic pain. Pain severity and frequency vary significantly among SCD patients. In this study, we investigated the possible contribution of monoamine gene polymorphisms to pain variation. Methods Adult subjects with SCD completed PAINReportIt®, a computerized McGill Pain Questionnaire, from which we calculated the Composite Pain Index. Utilization data were obtained from the medical record and biweekly telephone calls for 12 months. Utilization is defined as admissions to the emergency department and/or the acute care center resulting from a sickle cell pain crisis. We performed genotyping for catechol-O-methyltransferase (COMT) Val158Met (rs4680) and dopamine D3 receptor(DRD3) Ser9Gly (rs6280) polymorphisms, which were analyzed for associations with pain phenotypes. Results Binary logistic models revealed that DRD3 Ser9Gly heterozygote patients were more likely not to have an acute pain crisis (odds ratio [OR] [95% confidence interval (CI)], 4.37 [1.39, 22.89]; p=0.020), which remained so when demographic variables were considered (OR [95% CI], 4.53 [1.41, 28.58]; p=0.016). COMT Val158Met Met allele showed lower probability for zero utilization (OR [95% CI], 0.32 [0.12, 0.83]; p=0.020) than the Val allele. In the negative binomial regression analysis, subjects with COMT Met/Met genotype had utilization incident rate ratio [95% CI] of 2.20 [1.21, 3.99] over those with Val/Val (p=0.010). Conclusions These exploratory findings suggest that DRD3 Ser9Gly and COMT Val158Met may contribute to pain heterogeneity in SCD, as suggested by the different rates of acute pain crisis. Specifically, SCD patients with the DRD3 homozygote genotypes, COMT 158 Met allele or Met/Met genotype are more likely to have acute care utilization, an indicator of acute pain. These results, however, will need to be further examined in

  15. Catechol-O-methyltransferase Val158Met genotype in healthy and personality disorder individuals: Preliminary results from an examination of cognitive tests hypothetically differentially sensitive to dopamine functions

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    Winnie W Leung

    2007-01-01

    Full Text Available Winnie W Leung1, Margaret M McClure1, Larry J Siever1,2, Deanna M Barch3, Philip D Harvey1,21Department of Veterans Affairs, VISN 3 Mental Illness Research, Education, and Clinical Center (MIRECC, Bronx, NY, USA; 2Department of Psychiatry, Mt. Sinai School of Medicine, New York, NY, USA; 3Departments of Psychology and Psychiatry, Washington University, St. Louis, MO, USAAbstract: A functional polymorphism of the gene coding for Catechol-O-methyltrasferase (COMT, an enzyme responsible for the degradation of the catecholamine dopamine (DA, epinephrine, and norepinephrine, is associated with cognitive deficits. However, previous studies have not examined the effects of COMT on context processing, as measured by the AX-CPT, a task hypothesized to be maximally relevant to DA function. 32 individuals who were either healthy, with schizotypal personality disorder, or non-cluster A, personality disorder (OPD were genotyped at the COMT Val158Met locus. Met/Met (n = 6, Val/Met (n = 10, Val/Val (n = 16 individuals were administered a neuropsychological battery, including the AX-CPT and the N-back working memory test. For the AX-CPT, Met/Met demonstrated more AY errors (reflecting good maintenance of context than the other genotypes, who showed equivalent error rates. Val/Val demonstrated disproportionately greater deterioration with increased task difficulty from 0-back to 1-back working memory demands as compared to Met/Met, while Val/Met did not differ from either genotypes. No differences were found on processing speed or verbal working memory. Both context processing and working memory appear related to COMT genotype and the AX-CPT and N-back may be most sensitive to the effects of COMT variation.Keywords: COMT, dopamine, context processing, working memory, schizotypal personality disorder

  16. Effect of catechol-O-methyltransferase-val158met-polymorphism on the automatization of motor skills - a post hoc view on an experimental data.

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    Krause, Daniel; Beck, Frieder; Agethen, Manfred; Blischke, Klaus

    2014-06-01

    The purpose of this study was to evaluate if the catechol-O-methyltransferase-val158met (COMT)-polymorphism, which is known to affect prefrontal dopaminergic metabolism, affects the automatization of motor skills. Twenty-two participants volunteered for gene analysis after they had participated in experiments in which they practiced a single-joint arm movement sequence 460-760 times under different feedback conditions. Motor automaticity was assessed in a pre-test and a post-test according to the dual-task paradigm, which incorporated a visuo-spatial secondary task. To account for the different practice conditions in the four original studies, dual-task cost reduction was assessed using single case effect sizes proportioned to the respective group mean. For the secondary task but not for the prioritized motor task, these relative single case effect sizes proved to be positively (and significantly) correlated with the number of met-alleles on the COMT-genotype, rs=.553; p=.004. Thus, the number of met-alleles indicated a tendency toward enhanced motor automatization. Thus, due to an increased prefrontal dopamine level, met-carriers may be able to develop a well formed and stable, spatially coded movement representation early in practice, thereby supporting the formation of a representation in motor coordinates in the course of extended practice, which later enables automatic movement execution. This process might also be enhanced by a prevalence of met-carriers to functionally evaluate positive feedback information (i.e., rewards) and to better maintain recent reward information in active working memory.

  17. The COMT Val158 allele is associated with impaired delayed-match-to-sample performance in ADHD

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    Matthews Natasha

    2012-05-01

    Full Text Available Abstract Background This study explored the association between three measures of working memory ability and genetic variation in a range of catecholamine genes in a sample of children with ADHD. Methods One hundred and eighteen children with ADHD performed three working memory measures taken from the CANTAB battery (Spatial Span, Delayed-match-to-sample, and Spatial Working Memory. Associations between performance on working memory measures and allelic variation in catecholamine genes (including those for the noradrenaline transporter [NET1], the dopamine D4 and D2 receptor genes [DRD4; DRD2], the gene encoding dopamine beta hydroxylase [DBH] and catechol-O-methyl transferase [COMT] were investigated using regression models that controlled for age, IQ, gender and medication status on the day of test. Results Significant associations were found between performance on the delayed-match-to-sample task and COMT genotype. More specifically, val/val homozygotes produced significantly more errors than did children who carried a least one met allele. There were no further associations between allelic variants and performance across the other working memory tasks. Conclusions The working memory measures employed in the present study differed in the degree to which accurate task performance depended upon either the dynamic updating and/or manipulation of items in working memory, as in the spatial span and spatial working memory tasks, or upon the stable maintenance of representations, as in the delay-match–to-sample task. The results are interpreted as evidence of a relationship between tonic dopamine levels associated with the met COMT allele and the maintenance of stable working memory representations required to perform the delayed-match-to-sample-task.

  18. Association study between COMT 158Met and creativity scores in bipolar disorder and healthy controls

    OpenAIRE

    2014-01-01

    Background Bipolar disorder (BD) patients have been reported to be associated higher creativity abilities, and recent data tend to support the hypothesis that dopaminergic system that could be associated with creativity. Catechol-O-methyltransferase (COMT) is one of the major enzymes involved in the metabolic degradation of dopamine. The COMT gene polymorphism (rs4680 or Val158Met) Met allele is reported to cause decreased activity of this enzyme in prefrontal cortex and improve performance ...

  19. Catechol-O-methyltransferase Val158Met genotype and the clinical responses to duloxetine treatment or plasma levels of 3-methoxy-4-hydroxyphenylglycol and homovanillic acid in Japanese patients with major depressive disorder

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    Atake, Kiyokazu; Yoshimura, Reiji; Hori, Hikaru; Katsuki, Asuka; Nakamura, Jun

    2015-01-01

    Purpose This study investigated the relationships among the plasma levels of catecholamine metabolites, the clinical response to duloxetine treatment, and Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene. Subjects and methods Sixty-four patients and 30 healthy control subjects were recruited. Major depressive episodes were diagnosed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. The severity of depression was evaluated using the 17-item Hamilton Rating Scale for Depression (HAMD17). Patients whose HAMD17 scores were 15 or greater were enrolled in the study. Blood sampling and clinical evaluation were performed at week 0 and week 8. The levels of plasma catecholamine metabolites were measured using high-performance liquid chromatography with electrochemical detection. Genotyping was performed using direct sequencing. Results Thirty of 45 patients (67%) responded to duloxetine treatment during the 8 weeks of treatment. The baseline plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG), but not homovanillic acid (HVA), were lower in patients with major depressive disorder (MDD) who had the Val/Val genotype than in patients who were Met-carriers. Patients with MDD and the Val/Val genotype, but not Met carriers, had increased plasma levels of MHPG after 8 weeks of duloxetine treatment. The baseline plasma MHPG levels in healthy control subjects with the Val/Val genotype were significantly higher than those in patients with MDD. Among the subjects in the MDD group with the Val/Val genotype, the plasma MHPG levels increased to the same degree as in the healthy control subjects with the Val/Val genotype after 8 weeks of duloxetine treatment. Conclusion The relationship among the COMT Val158Met polymorphism, plasma levels of catecholamine metabolites, and responses to duloxetine is complex. Nevertheless, our results suggest that patients with MDD and the

  20. Voxelwise eigenvector centrality mapping of the human functional connectome reveals an influence of the catechol-O-methyltransferase val158met polymorphism on the default mode and somatomotor network.

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    Markett, Sebastian; Montag, Christian; Heeren, Behrend; Saryiska, Rayna; Lachmann, Bernd; Weber, Bernd; Reuter, Martin

    2016-06-01

    Functional connections between brain regions constitute the substrate of the human functional connectome, whose topography has been discussed as an endophenotype for psychiatric disorders. Genetic influences on the entire connectome, however, have been rarely investigated so far. We tested for connectome-wide influences of the val158met (rs4860) polymorphism on the catechol-O-methyltransferase (COMT) gene by applying formal network analysis and eigenvector centrality mapping on the voxel level to resting-state functional magnetic imaging data. This approach finds brain regions that are central in the network by aggregating local and global connectivity patterns, most importantly without the requirement to select regions or networks of interest. The COMT variant linked to high enzyme activity increased network centrality in distributed brain areas that are known to constitute the brain's default mode network. Further results also indicated a COMT influence on areas implicated in the somatomotor network. These findings are in line with the polymorphism's alleged role in cognitive processing and its role in psychotic disorders. The study is the first to demonstrate the influence of a functional and behaviorally relevant genetic variant on connectome-wide functional connectivity and is an important step toward establishing the functional connectome as an endophenotype for psychiatric and behavioral phenotypes.

  1. Catechol-O-methyltransferase Val158Met genotype and the clinical responses to duloxetine treatment or plasma levels of 3-methoxy-4-hydroxyphenylglycol and homovanillic acid in Japanese patients with major depressive disorder

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    Atake K

    2015-04-01

    Full Text Available Kiyokazu Atake, Reiji Yoshimura, Hikaru Hori, Asuka Katsuki, Jun Nakamura Department of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan Purpose: This study investigated the relationships among the plasma levels of catecholamine metabolites, the clinical response to duloxetine treatment, and Val158Met polymorphism of the catechol-O-methyltransferase (COMT gene. Subjects and methods: Sixty-four patients and 30 healthy control subjects were recruited. Major depressive episodes were diagnosed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. The severity of depression was evaluated using the 17-item Hamilton Rating Scale for Depression (HAMD17. Patients whose HAMD17 scores were 15 or greater were enrolled in the study. Blood sampling and clinical evaluation were performed at week 0 and week 8. The levels of plasma catecholamine metabolites were measured using high-performance liquid chromatography with electrochemical detection. Genotyping was performed using direct sequencing. Results: Thirty of 45 patients (67% responded to duloxetine treatment during the 8 weeks of treatment. The baseline plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG, but not homovanillic acid (HVA, were lower in patients with major depressive disorder (MDD who had the Val/Val genotype than in patients who were Met-carriers. Patients with MDD and the Val/Val genotype, but not Met carriers, had increased plasma levels of MHPG after 8 weeks of duloxetine treatment. The baseline plasma MHPG levels in healthy control subjects with the Val/Val genotype were significantly higher than those in patients with MDD. Among the subjects in the MDD group with the Val/Val genotype, the plasma MHPG levels increased to the same degree as in the healthy control subjects with the Val/Val genotype after 8 weeks of duloxetine treatment. Conclusion: The

  2. Association of Catechol-O-Methyltransferase (COMT) Polymorphism and Academic Achievement in a Chinese Cohort

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    Yeh, Ting-Kuang; Chang, Chun-Yen; Hu, Chung-Yi; Yeh, Ting-Chi; Lin, Ming-Yeh

    2009-01-01

    Catechol-O-methyltransferase (COMT) is a methylation enzyme that catalyzes the degradation pathway and inactivation of dopamine. It is accepted widely as being involved in the modulation of dopaminergic physiology and prefrontal cortex (PFC) function. The COMT Val158Met polymorphism is associated with variation in COMT activity. COMT 158Met allele…

  3. Association study between COMT 158Met and creativity scores in bipolar disorder and healthy controls

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    Márcio Gerhardt Soeiro-de-Souza

    2014-03-01

    Full Text Available Background Bipolar disorder (BD patients have been reported to be associated higher creativity abilities, and recent data tend to support the hypothesis that dopaminergic system that could be associated with creativity. Catechol-O-methyltransferase (COMT is one of the major enzymes involved in the metabolic degradation of dopamine. The COMT gene polymorphism (rs4680 or Val158Met Met allele is reported to cause decreased activity of this enzyme in prefrontal cortex and improve performance in several cognitive domains. Objective The objective of this study was to evaluate the influence of Val158Met on creativity in BD type I and healthy controls. Methods Ninety-seven healthy volunteers and 120 BD type I were genotyped for COMT rs4680 and tested for creativity (Barrow Welsh Art Scale – BWAS and intelligence Wechsler Abbreviated Scale of Intelligence (WASI. Results COMT Met allele positively influenced creativity scores in healthy controls but not in BD subjects during mood episodes and euthymia. The presence of allele Met did not influence IQ scores. No influence of IQ total score on creativity was observed. Limitations control group presented higher IQ scores and euthymic group was under medication use. Discussion Our research suggests positive effect of COMT rs4680 (allele Met on creativity scores in healthy controls. One possible interpretation is that creativity is more likely to be associated with lesser degrees of bipolarity. The fact that the same results were not observed in BD may be associated to dysfunctions in the dopaminergic system that characterizes this disorder. Further studies with larger samples and other types of BD should explore the role of the dopaminergic system in creativity.

  4. The Role of the Catechol-O-Methyltransferase (COMT) Gene in Personality and Related Psychopathological Disorders

    OpenAIRE

    Montag, Christian; Jurkiewicz, Magdalena; Reuter, Martin

    2012-01-01

    This review provides a short overview of the most significant biologically oriented theories of human personality. Personality concepts of Eysenck, Gray and McNaughton, Cloninger and Panksepp will be introduced and the focal evidence for the heritability of personality will be summarized. In this context, a synopsis of a large number of COMT genetic association studies (with a focus on the COMT Val158Met polymorphism) in the framework of the introduced biologically oriented personality theori...

  5. Hypnotizability and Catechol-O-Methyltransferase (COMT) polymorphysms in Italians

    Science.gov (United States)

    Presciuttini, Silvano; Gialluisi, Alessandro; Barbuti, Serena; Curcio, Michele; Scatena, Fabrizio; Carli, Giancarlo; Santarcangelo, Enrica L.

    2014-01-01

    Higher brain dopamine content depending on lower activity of Catechol-O-Methyltransferase (COMT) in subjects with high hypnotizability scores (highs) has been considered responsible for their attentional characteristics. However, the results of the previous genetic studies on association between hypnotizability and the COMT single nucleotide polymorphism (SNP) rs4680 (Val158Met) were inconsistent. Here, we used a selective genotyping approach to re-evaluate the association between hypnotizability and COMT in the context of a two-SNP haplotype analysis, considering not only the Val158Met polymorphism, but also the closely located rs4818 SNP. An Italian sample of 53 highs, 49 low hypnotizable subjects (lows), and 57 controls, were genotyped for a segment of 805 bp of the COMT gene, including Val158Met and the closely located rs4818 SNP. Our selective genotyping approach had 97.1% power to detect the previously reported strongest association at the significance level of 5%. We found no evidence of association at the SNP, haplotype, and diplotype levels. Thus, our results challenge the dopamine-based theory of hypnosis and indirectly support recent neuropsychological and neurophysiological findings reporting the lack of any association between hypnotizability and focused attention abilities. PMID:24431998

  6. Hypnotizability and Catechol-O-Methyltransferase (COMT polymorphysms in Italians

    Directory of Open Access Journals (Sweden)

    Silvano ePresciuttini

    2014-01-01

    Full Text Available Higher brain dopamine content depending on lower activity of Catechol-O-Methyltransferase (COMT in subjects with high hypnotisability scores (highs has been considered responsible for their attentional characteristics. However, the results of the previous genetic studies on association between hypnotisability and the Catechol-O-Methyltransferase (COMT single nucleotide polymorphism (SNP rs4680 (Val158Met were inconsistent. Here, we used a selective genotyping approach to re-evaluate the association between hypnotisability and COMT in the context of a two-SNP haplotype analysis, considering not only the Val158Met polymorphism, but also the closely located rs4818 SNP. An Italian sample of 53 highs, 49 low hypnotizable subjects (lows and 57 controls, were genotyped for a segment of 805 bp of the COMT gene, including Val158Met and the closely located rs4818 SNP. Our selective genotyping approach had 97.1% power to detect the previously reported strongest association at the significance level of 5%. We found no evidence of association at the SNP, haplotype and diplotype levels. Thus, our results challenge the dopamine-based theory of hypnosis and indirectly support recent neuropsychological and neurophysiological findings reporting the lack of any association between hypnotisability and focused attention abilities.

  7. Perception of emotion in facial stimuli: The interaction of ADRA2A and COMT genotypes, and sex.

    Science.gov (United States)

    Tamm, Gerly; Kreegipuu, Kairi; Harro, Jaanus

    2016-01-04

    Emotional facial stimuli are important social signals that are essential to be perceived and recognized in order to make appropriate decisions and responses in everyday communication. The ability to voluntarily guide attention to perceive and recognize emotions, and react to them varies largely across individuals, and has a strong genetic component (Friedman et al., 2008). Two key genetic variants of the catecholamine system that have been related to emotion perception and attention are the catechol-O-methyl transferase genetic variant (COMT Val158Met) and the α2A-receptor gene promoter polymorphism (ADRA2A C-1291G) accordingly. So far, the interaction of the two with sex in emotion perception has not been studied. Multilevel modeling method was applied to study how COMT Val158Met, ADRA2A C-1291G and sex are associated with measures of emotion perception in a large sample of young adults. Participants (n=506) completed emotion recognition and behavioral emotion detection tasks. It was found that COMT Val158Met genotype in combination with the ADRA2A C-1291G and sex predicts emotion detection, and perception of valence and arousal. In simple visual detection, the ADRA2A C-1291G G-allele leads to slower detection of a highly arousing face (scheming), which is modulated by each additional COMT Val158Met Met-allele and male sex predicting faster responses. The combination of G-allele, Met-allele and male sex also predicts higher perceived negativity in sad faces. No effects of C-1291G, Val158Met, and sex were found on verbal emotion recognition. Applying the findings to study the interplay between catecholamine-O-methyl transferase activity and α2A-receptors in emotion perception disorders (such as ADHD, autism and schizophrenia) in men and women would be the next step towards understanding individual differences in emotion perception.

  8. [The association of COMT and DRD2 gene polymorphisms with a cognitive ability to understand others in schizophrenic patients].

    Science.gov (United States)

    Alfimova, M V; Golimbet, V E; Korovaĭtseva, G I; Aksenova, E V; Lezheĭko, T V; Abramova, L I; Kolesina, N Iu; Anua, I M; Savel'eva, T M

    2013-01-01

    To evaluate a role of dopamine transmission in the theory of mind (ToM) dysfunction in schizophrenia, authors studied the association of ToM with COMT and DRD2 gene polymorphisms in 209 patients with schizophrenia and 172 healthy people. All subjects performed second-order false belief (FB2) and faux pas stories. The association between the COMT Val158Met polymorphism and performance on FB2 was found. The association was sex-specific. The worse performance was associated with a Met allele in female patients and with the ValVal genotype in male ones. A correlation analysis of the COMT Val158Met polymorphism, performance on FB2 task, neurocognitive and clinical symptoms suggests that in female patients the association was modified, in part, by the higher stress sensitivity caused by the severity of clinical symptoms and its consequences for cognitive functioning.

  9. Cortical Dopamine Transmission as Measured with the [11C]FLB 457 - Amphetamine PET Imaging Paradigm Is Not Influenced by COMT Genotype.

    Directory of Open Access Journals (Sweden)

    Rajesh Narendran

    Full Text Available Basic investigations link a Val158Met polymorphism (rs4680 in the catechol-O-methyltransferase (COMT gene to not only its enzymatic activity, but also to its dopaminergic tone in the prefrontal cortex. Previous PET studies have documented the relationship between COMT Val158Met polymorphism and D1 and D2/3 receptor binding potential (BP, and interpreted them in terms of dopaminergic tone. The use of baseline dopamine D1 and D2/3 receptor binding potential (BPND as a proxy for dopaminergic tone is problematic because they reflect both endogenous dopamine levels (a change in radiotracer's apparent affinity and receptor density. In this analysis of 31 healthy controls genotyped for the Val158Met polymorphism (Val/Val, Val/Met, and Met/Met, we used amphetamine-induced displacement of [11C]FLB 457 as a direct measure of dopamine release. Our analysis failed to show a relationship between COMT genotype status and prefrontal cortical dopamine release. COMT genotype was also not predictive of baseline dopamine D2/3 receptor BPND.

  10. Association of single nucleotide polymorphisms in CYP1B1 and COMT genes with breast cancer susceptibility in Indian women.

    Science.gov (United States)

    Yadav, Sharawan; Singhal, Naveen Kumar; Singh, Virendra; Rastogi, Neeraj; Srivastava, Pramod Kumar; Singh, Mahendra Pratap

    2009-01-01

    Cytochrome P450 1B1 (CYP1B1) and catechol-O-methyltransferase (COMT) enzymes play critical roles in estrogen metabolism. Alterations in the catalytic activity of CYP1B1 and COMT enzymes have been found associated with altered breast cancer risk in postmenopausal women in many populations. The substitution of leucine (Leu) to valine (Val) at codon 432 increases the catalytic activity of CYP1B1, however, substitution of Val to methionine (Met) at codon 158 decreases the catalytic activity of COMT. The present study was performed to evaluate the associations of CYP1B1 Leu(432)Val and/or COMT Val(158)Met polymorphisms with total, premenopausal and postmenopausal breast cancer risks in Indian women. COMT and CYP1B1 polymorphisms in controls and breast cancer patients were analyzed employing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) followed by gel electrophoresis. Although CYP1B1 and COMT genotypes did not exhibit statistically significant association with breast cancer risks when analyzed individually, COMT wild type (Val(158)Val) in combination with CYP1B1 heterozygous variant (Leu(432)Val) [OR: 0.21; 95% CI (0.05-0.82), p value; 0.021] and COMT heterozygous variant (Val(158)Met) in combination with CYP1B1 wild type (Leu(432)Leu) [OR: 0.29; 95% CI (0.08-0.96), p value; 0.042] showed significant protective association with premenopausal breast cancer risk. The results demonstrate that CYP1B1 wild type in combination with COMT heterozygous or their inverse combination offer protection against breast cancer in premenopausal Indian women.

  11. Association of Single Nucleotide Polymorphisms in CYP1B1 and COMT Genes with Breast Cancer Susceptibility in Indian Women

    Directory of Open Access Journals (Sweden)

    Sharawan Yadav

    2009-01-01

    Full Text Available Cytochrome P450 1B1 (CYP1B1 and catechol-$O$-methyltransferase (COMT enzymes play critical roles in estrogen metabolism. Alterations in the catalytic activity of CYP1B1 and COMT enzymes have been found associated with altered breast cancer risk in postmenopausal women in many populations. The substitution of leucine (Leu to valine (Val at codon 432 increases the catalytic activity of CYP1B1, however, substitution of Val to methionine (Met at codon 158 decreases the catalytic activity of COMT. The present study was performed to evaluate the associations of CYP1B1 Leu432Val and/or COMT Val158Met polymorphisms with total, premenopausal and postmenopausal breast cancer risks in Indian women. COMT and CYP1B1 polymorphisms in controls and breast cancer patients were analyzed employing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP followed by gel electrophoresis. Although CYP1B1 and COMT genotypes did not exhibit statistically significant association with breast cancer risks when analyzed individually, COMT wild type (Val158Val in combination with CYP1B1 heterozygous variant (Leu432Val [OR: 0.21; 95% CI (0.05–0.82, p value; 0.021] and COMT heterozygous variant (Val158Met in combination with CYP1B1 wild type (Leu432Leu [OR: 0.29; 95% CI (0.08–0.96, p value; 0.042] showed significant protective association with premenopausal breast cancer risk. The results demonstrate that CYP1B1 wild type in combination with COMT heterozygous or their inverse combination offer protection against breast cancer in premenopausal Indian women.

  12. The quantification of COMT mRNA in post mortem cerebellum tissue: diagnosis, genotype, methylation and expression

    Directory of Open Access Journals (Sweden)

    Craig Ian W

    2006-02-01

    Full Text Available Abstract Background The COMT gene is located on chromosome 22q11, a region strongly implicated in the aetiology of several psychiatric disorders, in particular schizophrenia. Previous research has suggested that activity and expression of COMT is altered in schizophrenia, and is mediated by one or more polymorphisms within the gene, including the functional Val158Met polymorphism. Method In this study we examined the expression levels of COMT mRNA using quantitative RT-PCR in 60 post mortem cerebellum samples derived from individuals with schizophrenia, bipolar disorder, depression, and no history of psychopathology. Furthermore, we have examined the methylation status of two CpG sites in the promoter region of the gene. Results We found no evidence of altered COMT expression or methylation in any of the psychiatric diagnoses examined. We did, however, find evidence to suggest that genotype is related to COMT gene expression, replicating the findings of two previous studies. Specifically, val158met (rs165688; Val allele rs737865 (G allele and rs165599 (G allele all showed reduced expression (P COMT expression, with females exhibiting significantly greater levels of COMT mRNA. Conclusion The expression of COMT does not appear to be altered in the cerebellum of individuals suffering from schizophrenia, bipolar disorder or depression, but does appear to be influenced by single nucleotide polymorphisms within the gene.

  13. COMT and prenatal maternal smoking in associations with conduct problems and crime: the Pelotas 1993 birth cohort study

    OpenAIRE

    Angélica Salatino-Oliveira; Joseph Murray; Christian Kieling; Júlia Pasqualini Genro; Guilherme Polanczyk; Luciana Anselmi; Fernando Wehrmeister; Barros, Fernando C; Ana Maria Baptista Menezes; Luis Augusto Rohde; Mara Helena Hutz

    2016-01-01

    Conduct problems in childhood and adolescence are significant precursors of crime and violence in young adulthood. The purpose of the current study is to test the interaction between prenatal maternal smoking and COMT Val 158 Met in conduct problems and crime in the 1993 Pelotas Birth Cohort Study. Conduct problems were assessed through the parent version of the Strengths and Difficulties Questionnaire at ages 11 and 15 years. A translated version of a confidential self-report questionnaire w...

  14. Catechol-O-methyltransferase (COMT) gene modulates private self-consciousness and self-flexibility.

    Science.gov (United States)

    Wang, Bei; Ru, Wenzhao; Yang, Xing; Yang, Lu; Fang, Pengpeng; Zhu, Xu; Shen, Guomin; Gao, Xiaocai; Gong, Pingyuan

    2016-08-01

    Dopamine levels in the brain influence human consciousness. Inspired by the role of Catechol-O-methyltransferase (COMT) in inactivating dopamine in the brain, we investigated to what extent COMT could modulate individual's self-consciousness dispositions and self-consistency by genotyping the COMT Val158Met (rs4680) polymorphism and measuring self-consciousness and self-consistency and congruence in a college student population. The results indicated that COMT Val158Met polymorphism significantly modulated the private self-consciousness. The individuals with Val/Val genotype, corresponding to lower dopamine levels in the brain, were more likely to be aware of their feelings and beliefs. The results also indicated that this polymorphism modulated one's self-flexibility. The individuals with Val/Val genotype showed higher levels of stereotype in self-concept compared with those with Met/Met genotype. These findings suggest that COMT is a predictor of the individual differences in self-consciousness and self-flexibility.

  15. The enzymatic activities of brain catechol-O-methyltransferase (COMT) and methionine sulphoxide reductase are correlated in a COMT Val/Met allele-dependent fashion.

    Science.gov (United States)

    Moskovitz, Jackob; Walss-Bass, Consuelo; Cruz, Dianne A; Thompson, Peter M; Hairston, Jenaqua; Bortolato, Marco

    2015-12-01

    The enzyme catechol-O-methyltransferase (COMT) plays a primary role in the metabolism of catecholamine neurotransmitters and is implicated in the modulation of cognitive and emotional responses. The best characterized single nucleotide polymorphism (SNP) of the COMT gene consists of a valine (Val)-to-methionine (Met) substitution at codon 108/158. The Met-containing variant confers a marked reduction in COMT catalytic activity. We recently showed that the activity of recombinant COMT is positively regulated by the enzyme Met sulphoxide reductase (MSR), which counters the oxidation of Met residues of proteins. The current study was designed to assess whether brain COMT activity may be correlated to MSR in an allele-dependent fashion. COMT and MSR activities were measured from post-mortem samples of prefrontal cortices, striata and cerebella of 32 subjects by using catechol and dabsyl-Met sulphoxide as substrates, respectively. Allelic discrimination of COMT Val(108/185) Met SNP was performed using the Taqman 5'nuclease assay. Our studies revealed that, in homozygous carriers of Met, but not Val alleles, the activity of COMT and MSR was significantly correlated throughout all tested brain regions. These results suggest that the reduced enzymatic activity of Met-containing COMT may be secondary to Met sulphoxidation and point to MSR as a key molecular determinant for the modulation of COMT activity. © 2015 British Neuropathological Society.

  16. The association study of polymorphisms in DAT, DRD2, and COMT genes and acute extrapyramidal adverse effects in male schizophrenic patients treated with haloperidol.

    Science.gov (United States)

    Zivković, Maja; Mihaljević-Peles, Alma; Bozina, Nada; Sagud, Marina; Nikolac-Perkovic, Matea; Vuksan-Cusa, Bjanka; Muck-Seler, Dorotea

    2013-10-01

    Extrapyramidal symptoms (EPSs) are common adverse effects of antipsychotics. The development of acute EPSs could depend on the activity of dopaminergic system and its gene variants. The aim of this study was to determine the association between dopaminergic type 2 receptor (DRD2) dopamine transporter (SLC6A3) and catechol-O-methyltransferase (COMT) gene polymorphisms and acute EPSs in 240 male schizophrenic patients treated with haloperidol (15-mg/d) over a period of 2 weeks. Acute EPSs were assessed with Simpson-Angus Scale. Three dopaminergic gene polymorphisms, the DRD2 Taq1A, the SLC6A3 VNTR, and the COMT Val158Met, were determined. Extrapyramidal symptoms occurred in 116 (48.3%) of patients. Statistically significant associations were found for SLC6A3 VNTR and COMT Val158Met polymorphisms and EPS susceptibility. Patients with SLC6A3 9/10 genotype had almost twice the odds to develop EPSs compared with those with all other SLC6A3 genotypes (odds ratio, 1.9; 95% confidence interval, 1.13-3.30), and patients with COMT Val/Met genotype had 1.7 times greater odds to develop EPSs than those with all other COMT genotypes (odds ratio, 1.7; 95% confidence interval, 1.01-2.88). There was no statistically significant association between genotype and allele frequencies of DRD2, SLC6A3, or COMT polymorphisms and the development of particular EPSs.In conclusion, the results of the present study showed for the first time the association between acute haloperidol-induced EPSs and SLC6A3 VNTR and COMT Val158Met polymorphisms. Although the precise biological mechanisms underlying these findings are not yet understood, the results suggest that the dopaminergic gene variations could predict the vulnerability to the development of the acute EPSs in haloperidol-treated schizophrenic patients.

  17. Differential Genetic and Epigenetic Regulation of Catechol-O-Methyl-Transferase (COMT is Associated with Impaired Fear Inhibition in Posttraumatic Stress Disorder

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    Seth Davin Norrholm

    2013-04-01

    Full Text Available The catechol-O-methyltransferase (COMT enzyme is critical for the catabolic regulation of synaptic dopamine, resulting in altered cortical functioning. The COMT Val158Met polymorphism has been implicated in human mental illness, with Met/Met homozygotes associated with increased susceptibility to posttraumatic stress disorder (PTSD. Our primary objective was to examine the intermediate phenotype of fear inhibition in PTSD stratified by COMT genotype (Met/Met, Val/Met, and Val/Val and differential gene regulation via methylation status at CpG sites in the COMT promoter region. More specifically, we examined the potential interaction of COMT genotype and PTSD diagnosis on fear-potentiated startle during fear conditioning and extinction and COMT DNA methylation levels (as determined using genomic DNA isolated from whole blood . Participants were recruited from medical and gynecological clinics of an urban hospital in Atlanta, Georgia. We found that individuals with the Met/Met genotype demonstrated higher fear-potentiated startle to the CS- (safety signal and during extinction of the CS+ (danger signal compared to Val/Met and Val/Val genotypes. The PTSD+ Met/Met genotype group had the greatest impairment in fear inhibition to the CS- (p=.006, compared to Val carriers. In addition, the Met/Met genotype was associated with DNA methylation at 4 CpG sites, 2 of which were associated with impaired fear inhibition to the safety signal. These results suggest that multiple differential mechanisms for regulating COMT function – at the level of protein structure via the Val158Met genotype and at the level of gene regulation via differential methylation - are associated with impaired fear inhibition in PTSD.

  18. COMT Val108/158 Met Genotype Affects Neural but not Cognitive Processing in Healthy Individuals

    Science.gov (United States)

    Need, Anna C.; LaBar, Kevin S.; Waters-Metenier, Sheena; Cirulli, Elizabeth T.; Kragel, James; Goldstein, David B.; Cabeza, Roberto

    2010-01-01

    The relationship between cognition and a functional polymorphism in the catechol-O-methlytransferase (COMT) gene, val108/158met, is one of debate in the literature. Furthermore, based on the dopaminergic differences associated with the COMT val108/158met genotype, neural differences during cognition may be present, regardless of genotypic differences in cognitive performance. To investigate these issues the current study aimed to 1) examine the effects of COMT genotype using a large sample of healthy individuals (n = 496–1218) and multiple cognitive measures, and using a subset of the sample (n = 22), 2) examine whether COMT genotype effects medial temporal lobe (MTL) and frontal activity during successful relational memory processing, and 3) investigate group differences in functional connectivity associated with successful relational memory processing. Results revealed no significant group difference in cognitive performance between COMT genotypes in any of the 19 cognitive measures. However, in the subset sample, COMT val homozygotes exhibited significantly decreased MTL and increased prefrontal activity during both successful relational encoding and retrieval, and reduced connectivity between these regions compared with met homozygotes. Taken together, the results suggest that although the COMT val108/158met genotype has no effect on cognitive behavioral measures in healthy individuals, it is associated with differences in neural process underlying cognitive output. PMID:19641018

  19. Adipose tissue PCB levels and CYP1B1 and COMT genotypes in relation to breast cancer risk in postmenopausal Danish women

    DEFF Research Database (Denmark)

    Bräuner, Elvira; Loft, Steffen; Wellejus, Anja

    2014-01-01

    these enzymes control efficiency. Our objective was to assess whether CYP1B1 and COMT gene polymorphisms modulate the effect of PCBs in breast cancer risk, among postmenopausal Danish women. Neither CYP1B1 Leu432Val polymorphisms nor adipose tissue PCBs were independently associated with breast cancer risk....... When assessing the independent effect of the COMT Val158Met polymorphism, we observed reduced risk for breast cancer amongst hormone replacement therapy using women who were homozygous carriers of the variant allele compared with those carrying the wild-type variant (RR = 0.41; 95% CI: 0.29-0.89). We...

  20. How to consistently link extraversion and intelligence to the catechol-O-methyltransferase (COMT) gene: on defining and measuring psychological phenotypes in neurogenetic research.

    Science.gov (United States)

    Wacker, Jan; Mueller, Erik M; Hennig, Jürgen; Stemmler, Gerhard

    2012-02-01

    The evidence for associations between genetic polymorphisms and complex behavioral/psychological phenotypes (traits) has thus far been weak and inconsistent. Using the well-studied Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene as an example, we demonstrate that using theoretical models to guide phenotype definition and measuring the phenotypes of interest with a high degree of specificity reveals strong gene-behavior associations that are consistent with prior work and that would have otherwise gone unnoticed. Only after statistically controlling for irrelevant portions of phenotype variance did we observe strong (Cohen's d = 0.33-0.70) and significant associations between COMT Val158Met and both cognitive and affective traits in a healthy male sample (N = 201) in Study 1: Carriers of the Met allele scored higher in fluid intelligence (reasoning) but lower in both crystallized intelligence (general knowledge) and the agency facet of extraversion. In Study 2, we conceptually replicated the association of COMT Val158Met with the agency facet of extraversion after partialing irrelevant phenotype variance in a female sample (N = 565). Finally, through reanalysis of a large published data set we showed that Met allele carriers also scored higher in indicators of fluid intelligence after partialing verbal fluency. Because the Met allele codes for a less efficient variant of the enzyme COMT, resulting in higher levels of extrasynaptic prefrontal dopamine, these observations provide further support for a role for dopamine in both intelligence and extraversion. More importantly, the present findings have important implications for the definition of psychological phenotypes in neurogenetic research.

  1. Count on dopamine: influences of COMT polymorphisms on numerical cognition

    Science.gov (United States)

    Júlio-Costa, Annelise; Antunes, Andressa M.; Lopes-Silva, Júlia B.; Moreira, Bárbara C.; Vianna, Gabrielle S.; Wood, Guilherme; Carvalho, Maria R. S.; Haase, Vitor G.

    2013-01-01

    Catechol-O-methyltransferase (COMT) is an enzyme that is particularly important for the metabolism of dopamine. Functional polymorphisms of COMT have been implicated in working memory and numerical cognition. This is an exploratory study that aims at investigating associations between COMT polymorphisms, working memory, and numerical cognition. Elementary school children from 2th to 6th grades were divided into two groups according to their COMT val158met polymorphism [homozygous for valine allele (n = 61) vs. heterozygous plus methionine homozygous children or met+ group (n = 94)]. Both groups were matched for age and intelligence. Working memory was assessed through digit span and Corsi blocks. Symbolic numerical processing was assessed through transcoding and single-digit word problem tasks. Non-symbolic magnitude comparison and estimation tasks were used to assess number sense. Between-group differences were found in symbolic and non-symbolic numerical tasks, but not in working memory tasks. Children in the met+ group showed better performance in all numerical tasks while val homozygous children presented slower development of non-symbolic magnitude representations. These results suggest COMT-related dopaminergic modulation may be related not only to working memory, as found in previous studies, but also to the development of magnitude processing and magnitude representations. PMID:23966969

  2. Count on dopamine: influences of COMT polymorphisms on numerical cognition

    Directory of Open Access Journals (Sweden)

    Annelise eJúlio-Costa

    2013-08-01

    Full Text Available Catechol-O-methyltransferase (COMT is an enzyme that is particularly important for the metabolism of dopamine. Functional polymorphisms of COMT have been implicated in working memory and numerical cognition. This is an exploratory study that aims at investigating associations between COMT polymorphisms, working memory and numerical cognition. Elementary school children from 2th to 6th grades were divided into two groups according to their COMT val158met polymorphism (homozygous for valine allele [n= 61] versus heterozygous plus methionine homozygous children or met+ group [n=94]. Both groups were matched for age and intelligence. Working memory was assessed through digit span and Corsi blocks. Symbolic numerical processing was assessed through transcoding and single-digit word problem tasks. Non-symbolic magnitude comparison and estimation tasks were used to assess number sense. Between-group differences were found in symbolic and non-symbolic numerical tasks, but not in working memory tasks. Children in the met+ group showed better performance in all numerical tasks while val homozygous children presented slower development of non-symbolic magnitude representations. These results suggest COMT-related dopaminergic modulation may be related not only to working memory, as found in previous studies, but also to the development of magnitude processing and magnitude representations.

  3. The role of the catechol-O-methyltransferase (COMT) gene in personality and related psychopathological disorders.

    Science.gov (United States)

    Montag, Christian; Jurkiewicz, Magdalena; Reuter, Martin

    2012-05-01

    This review provides a short overview of the most significant biologically oriented theories of human personality. Personality concepts of Eysenck, Gray and McNaughton, Cloninger and Panksepp will be introduced and the focal evidence for the heritability of personality will be summarized. In this context, a synopsis of a large number of COMT genetic association studies (with a focus on the COMT Val158Met polymorphism) in the framework of the introduced biologically oriented personality theories will be given. In line with the theory of a continuum model between healthy anxious behavior and related psychopathological behavior, the role of the COMT gene in anxiety disorders will be discussed. A final outlook considers new research strategies such as genetic imaging and epigenetics for a better understanding of human personality.

  4. Synergistic effects of COMT and TPH2 on social cognition.

    Science.gov (United States)

    Lin, Chieh-Hsin; Tseng, Yu-Lun; Huang, Chieh-Liang; Chang, Yue-Cune; Tsai, Guochuan E; Lane, Hsien-Yuan

    2013-01-01

    Whether genetic factors affect social cognition, particularly emotion management, requires elucidation. This study investigates whether social cognition varies with genetic variations of COMT and tryptophan hydroxylase-2 (TPH2), which modulate dopamine and serotonin neurotransmissions respectively, and thereby emotion regulation. NIMH-recommended "managing emotions branch and 2 subtasks" of MSCEIT and six neurocognition domains, and genotypes of COMT Val158Met and TPH2 G703T were measured in 150 Han-Chinese healthy adults. Subjects carrying the M allele (M group) of COMT exceeded Val/Val homozygotes (V group) in managing emotions branch (p = 0.032) and emotional relation subtask (p = 0.037). TPH2 T/T homozygotes (T group) excelled those with the G allele (G group) in emotional management subtask (p = 0.025). Subjects with M+T variation surpassed the other 3 groups (M+G, V+T and V+G) in managing emotion branch (p = 0.002), emotional relation subtask (p = 0.023), and emotional management subtask (p = 0.002). The findings remained after control for gender, age, education, and neurocognitive functions. Synergistically, the effect size of COMT-TPH2 combination surmounted the sum of separate effect sizes of COMT and TPH2. The findings suggest that genetic variations of COMT and TPH2 have synergistic effects on social cognition in the general population.

  5. Progress on Association between COMT Gene and Violence Behavior in Patients with Schizophrenia%COMT基因与精神分裂症患者暴力攻击行为关联性的研究进展

    Institute of Scientific and Technical Information of China (English)

    张钦廷; 赵敏; 谢斌

    2014-01-01

    精神分裂症患者的暴力攻击行为发生率高于一般人群,暴力攻击行为在某些方面具有显著的遗传倾向性,与精神分裂症患者暴力攻击行为研究最多的是儿茶酚氧位甲基转移酶(catechol-O-methyltrans-ferase , COMT )基因。本文从COMT Val158MetCOMT Ala72Ser 的SNP 多态性、COMT 基因单倍型、COMT基因启动子区DNA甲基化等方面对COMT基因变异与精神分裂症患者暴力攻击行为的相关性研究进行综述,并提出精神分裂症患者暴力攻击行为的遗传学研究方向。%The prevalence of violence behavior in patients with schizophrenia is higher than that in common population. Data suggest that genetic factors may play a substantial role for the etiology of the behavior. Among the particular gene polymorphisms that have been considered to be involved in vio-lence behavior, the catechol-O-methyltransferase (COMT) gene had been the focus of recent research. This article reviews the association research between COMT gene and violence behavior in patients with schizophrenia in several aspects: SNP polymorphism of COMT Val158Met and COMT Ala72Ser, haplo-type of COMT gene and DNA methylation of promoter region of COMT gene. The genetic research di-rection is presented for patients with schizophrenia.

  6. Influence of COMT genotype and affective distractors on the processing of self-generated thought.

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    Kilford, Emma J; Dumontheil, Iroise; Wood, Nicholas W; Blakemore, Sarah-Jayne

    2015-06-01

    The catechol-O-methyltransferase (COMT) enzyme is a major determinant of prefrontal dopamine levels. The Val(158)Met polymorphism affects COMT enzymatic activity and has been associated with variation in executive function and affective processing. This study investigated the effect of COMT genotype on the flexible modulation of the balance between processing self-generated and processing stimulus-oriented information, in the presence or absence of affective distractors. Analyses included 124 healthy adult participants, who were also assessed on standard working memory (WM) tasks. Relative to Val carriers, Met homozygotes made fewer errors when selecting and manipulating self-generated thoughts. This effect was partly accounted for by an association between COMT genotype and visuospatial WM performance. We also observed a complex interaction between the influence of affective distractors, COMT genotype and sex on task accuracy: male, but not female, participants showed a sensitivity to the affective distractors that was dependent on COMT genotype. This was not accounted for by WM performance. This study provides novel evidence of the role of dopaminergic genetic variation on the ability to select and manipulate self-generated thoughts. The results also suggest sexually dimorphic effects of COMT genotype on the influence of affective distractors on executive function. © The Author (2014). Published by Oxford University Press.

  7. Modifying effect of COMT gene polymorphism and a predictive role for proteomics analysis in children's intelligence in endemic fluorosis area in Tianjin, China.

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    Zhang, Shun; Zhang, Xiaofei; Liu, Hongliang; Qu, Weidong; Guan, Zhizhong; Zeng, Qiang; Jiang, Chunyang; Gao, Hui; Zhang, Cheng; Lei, Rongrong; Xia, Tao; Wang, Zhenglun; Yang, Lu; Chen, Yihu; Wu, Xue; Cui, Yushan; Yu, Linyu; Wang, Aiguo

    2015-04-01

    Cumulative fluoride exposure has adverse influences on children's intelligence quotient (IQ). In addition, catechol-O-methyltransferase (COMT) gene Val158Met polymorphism (rs4680) is associated with cognitive performance. This study aimed to evaluate the associations of COMT polymorphism and alterations of protein profiles with children's intelligence in endemic fluorosis area. We recruited 180 schoolchildren (10-12 years old) from high fluoride exposure (1.40 mg/l) and control areas (0.63 mg/l) in Tianjin City, China. The children's IQ, fluoride contents in drinking water (W-F), serum (S-F), and urine (U-F); serum thyroid hormone levels, COMT Val158Met polymorphism, and plasma proteomic profiling were determined. Significant high levels of W-F, S-F, U-F, along with poor IQ scores were observed in the high fluoride exposure group compared with those in control (all P intelligence, whereas the COMT polymorphism may increase the susceptibility to the deficits in IQ due to fluoride exposure. Moreover, the proteomic analysis can provide certain basis for identifying the early biological markers of fluorosis among children. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Does COMT genotype influence the effects of d-amphetamine on executive functioning?

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    Wardle, M C; Hart, A B; Palmer, A A; de Wit, H

    2013-02-01

    In a widely cited study, Mattay et al. reported that amphetamine (0.25 mg/kg oral, or 17 mg for a 68 kg individual) impaired behavioral and brain indices of executive functioning, measured using the Wisconsin Card Sorting Task (WCST) and N-Back working memory task, in 6 individuals homozygous for the met allele of the val158met polymorphism in the catechol-O-methyltransferase (COMT) gene, whereas it improved executive functioning in 10 individuals homozygous for the more active val allele. We attempted to replicate their behavioral findings in a larger sample, using similar executive functioning tasks and a broader range of amphetamine doses. Over four sessions, n = 200 healthy normal adults received oral placebo, d-amphetamine 5, 10, and 20 mg (average of 0.07, 0.15 and 0.29 mg/kg), under counterbalanced double-blind conditions and completed WCST and N-back tests of executive functioning. Amphetamine had typical effects on blood pressure and processing speed but did not affect executive functioning. COMT genotype (val158met) was not related to executive functioning under placebo or amphetamine conditions, even when we compared only the homozygous val/val and met/met genotypes at the highest dose of amphetamine (20 mg). Thus, we were not able to replicate the behavioral interaction between COMT and amphetamine seen in Mattay et al. We discuss possible differences between the studies and the implications of our findings for the use of COMT genotyping to predict clinical responses to dopaminergic drugs, and the use of intermediate phenotypes in genetic research.

  9. COMT-by-Sex Interaction Effect on Psychosis Proneness

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    Marta de Castro-Catala

    2015-01-01

    Full Text Available Schizotypy phenotypes in the general population share etiopathogenic mechanisms and risk factors with schizophrenia, supporting the notion of psychosis as a continuum ranging from nonclinical to clinical deviance. Catechol-O-methyltransferase (COMT is a candidate susceptibility gene for schizophrenia that is involved in the regulation of dopamine in the prefrontal cortex. Several recent studies have reported a sex difference in the impact of COMT genotype on psychiatric and cognitive phenotypes and personality traits. The present study investigated the association of COMT Val158Met (rs4680 with psychometric positive and negative schizotypy and psychotic experiences in a sample of 808 nonclinical young adults. The main finding was that sex moderates the association of COMT genotype with the negative dimension of both schizotypy and psychotic experiences. Male subjects carrying the Val allele tended to score higher on the negative dimension of both trait and symptom-like measures. The results from the present study are consistent with recent work suggesting an association between negative schizotypy and diminished prefrontal dopamine availability. They support the idea that a biological differentiation underlies the positive and negative schizotypy dimensions. Additionally, these findings contribute to the growing literature on sex-specific effects of COMT on the predisposition to psychiatric disorders and personality traits.

  10. Evidence that COMT genotype and proline interact on negative-symptom outcomes in schizophrenia and bipolar disorder.

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    Clelland, C L; Drouet, V; Rilett, K C; Smeed, J A; Nadrich, R H; Rajparia, A; Read, L L; Clelland, J D

    2016-09-13

    Elevated peripheral proline is associated with psychiatric disorders, and there is evidence that proline is a neuromodulator. The proline dehydrogenase (PRODH) gene, which encodes the enzyme that catalyzes proline catabolism, maps to human chromosome 22q11.2, a region conferring risk of schizophrenia. In the Prodh-null mouse, an interaction between elevated peripheral proline and another 22q11.2 gene, catechol-O-methyltransferase (COMT), on neurotransmission and behavior has been reported. We explored the relationship between fasting plasma proline levels and COMT Val(158)Met genotype on symptoms (positive, negative and total) in schizophrenia patients. In an exploratory study we also examined symptom change in patients with bipolar disorder. There was a significant interaction between peripheral proline and COMT on negative symptoms in schizophrenia (P<0.0001, n=95). In COMT Val/Val patients, high proline was associated with low Scale for the Assessment of Negative Symptom (SANS) scores. In contrast, high proline was associated with high SANS scores in patients carrying a Met allele. The relationship between proline and COMT also appears to modify negative symptoms across psychiatric illness. In bipolar disorder, a significant interaction was also observed on negative-symptom change (P=0.007, n=43). Negative symptoms are intractable and largely unaddressed by current medications. These data indicate a significant interaction between peripheral proline and COMT genotype, influencing negative symptoms in schizophrenia and bipolar disorder. That high proline has converse effects on symptoms by COMT genotype, may have implications for therapeutic decisions.

  11. Distribution of the Val108/158Met polymorphism of the COMT gene in healthy Mexican population.

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    González-Castro, Thelma Beatriz; Tovilla-Zárate, Carlos; Juárez-Rojop, Isela; Pool García, Sherezada; Genis, Alma; Nicolini, Humberto; López Narváez, Lilia

    2013-09-10

    Catechol-O-methyltransferase (COMT) inactivates the catecholamines adrenaline, noradrenaline and dopamine. On the other hand, some studies have reported that the enzymatic activity of COMT is partly genetically determined. With regard to the COMT gene, the most studied polymorphism is the functional variant Val108/158Met (rs4680), which results in substantial three- to four-fold variations in enzyme activity. To date, the rs4680 polymorphism of COMT has been associated with a number of disorders. In addition, this polymorphism has been found to have important differences in frequency according to the studied population. Therefore, the aim of the present study was to evaluate the frequency of a common single nucleotide polymorphism (SNP) Val108/158Met of the COMT gene in the Mexican population. Accordingly, we recruited 431 healthy volunteers. Our sample consisted of 111 healthy individuals from Mexico City and 320 individuals from the state of Tabasco, Mexico. We observed that Met was the most common allele, ranging from 57% (Tabasco) to 85% (Mexico City). In addition, we analyzed the frequency of Val108/158Met polymorphism of Caucasian (54% Met allele), Asian (29% Met allele) and African (34% Met allele) populations separately and also in comparison with Mexican (63% Met allele) population. In conclusion, the distribution of the Val108/158Met polymorphism distinguishes the Mexican population studied from other populations, but it is necessary to increase the size of the sample to get more conclusive results.

  12. Child exposure to serious life events, COMT, and aggression: Testing differential susceptibility theory.

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    Hygen, Beate Wold; Belsky, Jay; Stenseng, Frode; Lydersen, Stian; Guzey, Ismail Cuneyt; Wichstrøm, Lars

    2015-08-01

    Both genetic and environmental factors contribute to individual differences in aggression. Catechol-O-methyltransferase Val158Met (COMT), a common, functional polymorphism, has been implicated in aggression and aggression traits, as have childhood experiences of adversity. It is unknown whether these effects are additive or interactional and, in the case of interaction, whether they conform to a diathesis-stress or differential susceptibility model. We examined Gene × Environment interactions between COMT and serious life events on measures of childhood aggression and contrasted these 2 models. The sample was composed of community children (N = 704); 355 were boys, and the mean age was 54.8 months (SD = 3.0). The children were genotyped for COMT rs4680 and assessed for serious life events and by teacher-rated aggression. Regression analysis showed no main effects of COMT and serious life events on aggression. However, a significant interactive effect of childhood serious life events and COMT genotype was observed: Children who had faced many serious life events and were Val homozygotes exhibited more aggression (p = .02) than did their Met-carrying counterparts. Notably, in the absence of serious life events, Val homozygotes displayed significantly lower aggression scores than did Met carriers (p = .03). When tested, this constellation of findings conformed to the differential susceptibility hypothesis: In this case, Val homozygotes are more malleable to the effect of serious life events on aggression and not simply more vulnerable to the negative effect of having experienced many serious life events.

  13. Genetic Variation in the Catechol-O-Methyl Transferase Val108/158Met Is Linked to the Caudate and Posterior Cingulate Cortex Volume in Healthy Subjects: Voxel-Based Morphometry Analysis of Brain Magnetic Resonance Imaging.

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    Keita Watanabe

    Full Text Available The effect of the catechol-O-methyltransferase (COMT Val158Met polymorphism on brain morphology has been investigated but remains controversial. We hypothesized that a comparison between Val/Val and Val/Met individuals, which may represent the most different combinations concerning the effects of the COMT genotype, may reveal new findings. We investigated the brain morphology using 3-Tesla magnetic resonance imaging in 27 Val/Val and 22 Val/Met individuals. Voxel-based morphometry revealed that the volumes of the bilateral caudate and posterior cingulate cortex were significantly smaller in Val/Val individuals than in Val/Met individuals [right caudate: false discovery rate (FDR-corrected p = 0.048; left caudate: FDR-corrected p = 0.048; and bilateral posterior cingulate cortex: FDR-corrected p = 0.048]. This study demonstrates that interacting functional variants of COMT affect gray matter regional volumes in healthy subjects.

  14. Genetic Variation in the Catechol-O-Methyl Transferase Val108/158Met Is Linked to the Caudate and Posterior Cingulate Cortex Volume in Healthy Subjects: Voxel-Based Morphometry Analysis of Brain Magnetic Resonance Imaging

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    Watanabe, Keita; Kakeda, Shingo; Yoshimura, Reiji; Ide, Satoru; Hayashi, Kenji; Katsuki, Asuka; Umene-Nakano, Wakako; Watanabe, Rieko; Abe, Osamu; Korogi, Yukunori

    2015-01-01

    The effect of the catechol-O-methyltransferase (COMT) Val158Met polymorphism on brain morphology has been investigated but remains controversial. We hypothesized that a comparison between Val/Val and Val/Met individuals, which may represent the most different combinations concerning the effects of the COMT genotype, may reveal new findings. We investigated the brain morphology using 3-Tesla magnetic resonance imaging in 27 Val/Val and 22 Val/Met individuals. Voxel-based morphometry revealed that the volumes of the bilateral caudate and posterior cingulate cortex were significantly smaller in Val/Val individuals than in Val/Met individuals [right caudate: false discovery rate (FDR)-corrected p = 0.048; left caudate: FDR-corrected p = 0.048; and bilateral posterior cingulate cortex: FDR-corrected p = 0.048]. This study demonstrates that interacting functional variants of COMT affect gray matter regional volumes in healthy subjects. PMID:26566126

  15. Genetic contributions to age-related decline in executive function: a 10-year longitudinal study of COMT and BDNF polymorphisms

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    Kirk I Erickson

    2008-09-01

    Full Text Available Genetic variability in the dopaminergic and neurotrophic systems could contribute to age-related impairments in executive control and memory function. In this study we examined whether genetic polymorphisms for catechol-O-methyltransferase (COMT and brain-derived neurotrophic factor (BDNF were related to the trajectory of cognitive decline occurring over a 10-year period in older adults. A single-nucleotide polymorphism (SNP in the COMT (Val158/108Met gene affects the concentration of dopamine in the prefrontal cortex. In addition, a Val/Met substitution in the pro-domain for BDNF (Val66Met affects the regulated secretion and trafficking of BDNF with Met carriers showing reduced secretion and poorer cognitive function. We found that impairments over the 10-year span on a task-switching paradigm did not vary as a function of the COMT polymorphism. However, for the BDNF polymorphism the Met carriers performed worse than Val homozygotes at the first testing session but only the Val homozygotes demonstrated a significant reduction in performance over the 10-year span. Our results argue that the COMT polymorphism does not affect the trajectory of age-related executive control decline, whereas the Val/Val polymorphism for BDNF may promote faster rates of cognitive decay in old age. These results are discussed in relation to the role of BDNF in senescence and the transforming impact of the Met allele on cognitive function in old age.

  16. Catechol-O-Methyltransferase (COMT Val108/158 Met polymorphism does not modulate executive function in children with ADHD

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    Stepanian Marina

    2004-12-01

    Full Text Available Abstract Background An association has been observed between the catechol-O-methyltransferase (COMT gene, the predominant means of catecholamine catabolism within the prefrontal cortex (PFC, and neuropsychological task performance in healthy and schizophrenic adults. Since several of the cognitive functions typically deficient in children with Attention Deficit Hyperactivity Disorder (ADHD are mediated by prefrontal dopamine (DA mechanisms, we investigated the relationship between a functional polymorphism of the COMT gene and neuropsychological task performance in these children. Methods The Val108/158 Met polymorphism of the COMT gene was genotyped in 118 children with ADHD (DSM-IV. The Wisconsin Card Sorting Test (WCST, Tower of London (TOL, and Self-Ordered Pointing Task (SOPT were employed to evaluate executive functions. Neuropsychological task performance was compared across genotype groups using analysis of variance. Results ADHD children with the Val/Val, Val/Met and Met/Met genotypes were similar with regard to demographic and clinical characteristics. No genotype effects were observed for WCST standardized perseverative error scores [F2,97 = 0.67; p > 0.05], TOL standardized scores [F2,99 = 0.97; p > 0.05], and SOPT error scores [F2,108 = 0.62; p > 0.05]. Conclusions Contrary to the observed association between WCST performance and the Val108/158 Met polymorphism of the COMT gene in both healthy and schizophrenic adults, this polymorphism does not appear to modulate executive functions in children with ADHD.

  17. Disorganization, COMT, and Children’s Social Behavior: The Norwegian Hypothesis of Legacy of Disorganized Attachment

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    Zhi Li

    2016-07-01

    Full Text Available Why is disorganized attachment associated with punitive-controlling behavior in some, but caregiving-controlling in others? Hygen and associates (2014 proposed that variation in the Catechol-O-methyl transferase(COMT Val158Met genotype explains this variation, providing preliminary data to this effect. We offer a conceptual replication, analyzing data on 560 children (males: 275 drawn from the NICHD Study of Early Child Care and Youth Development. As predicted, competitive model-fitting indicated that disorganized infants carrying Met alleles engage in more positive behavior and less negative behavior than other children at age 5 and 11, with the reverse true of Val/Val homozygotes, seemingly consistent with caregiving-controlling and punitive-controlling styles, respectively, but only in the case of maternal and not teacher reports, thereby confirmating a relationship-specific hypothesis.

  18. Pulse Pressure magnifies the effect of COMTVal158Met on 15 Year Episodic Memory Trajectories

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    Ninni ePersson

    2016-03-01

    Full Text Available We investigated whether a physiological marker of cardiovascular health, pulse pres­sure (PP, and age magnified the effect of the functional COMT Val158Met (rs4680 pol­ymor­phism on 15-year cognitive trajectories (episodic memory [EM], visuospatial ability, and se­man­tic memory using data from 1585 non-demented adults from the Betula study. A mul­tiple-group growth model was specified to gauge individual differences in change. The allelic variants showed negligible differences across the cognitive markers in average trends. The older portion of the sample selectively age-magnified the effects of Val158Met on EM changes, resulting in greater decline in Val compared to homozygote Met carriers. This effect was attenuated by sta­tistical control for PP. Further, PP mod­erated the effects of COMT on 15-year EM trajectories, resulting in greater decline in Val carriers, even after accounting for the confounding effects of sex, education, cardiovascular diseases (dia­betes, stroke, and hypertension, and chronological age, controlled for practice gains. The effect was still present after excluding individuals with a history of cardiovascular diseases. The effects of cognitive change were not moderated by any other covariates. This report underscores the importance of addressing synergistic effects in nor­mal cognitive aging, as the addition thereof may even place healthy individuals at greater risk for memory decline.

  19. Association of COMT gene polymorphisms with cerebral infarction in Han people of Tianjin

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    WANG Jin-huan

    2013-04-01

    Full Text Available Background Catechol-O-methyltransferase (COMT has a key function in thedegradation of catecholamines and inactivating estrogen. A common polymorphism in the COMT gene is guanine-adenine (G-A point mutation on rs4680, which causes a valine (Val substitution to methionine (Met in 108 and (or 158 amino acid by this gene and is responsible for lowered activity of the enzyme. The Val/Met polymorphism has been recognized to be associated with psychiatric disorders, alcohol dependence and drug side effects, but few study has been done to examine the relationship with cerebral infarction (CI. The objective of this study is to investigate the relationship between the polymorphisms of COMT gene and CI. Methods The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP was used to detect COMT Val158Met genotype in 181 CI patients and 148 cases of controls. Meanwhile the serum levels of glucose, total cholesterol (TC, triglyceride (TG, low-density lipoprotein cholesterol (LDL-C , high-density lipoprotein cholesterol (HDL-C , apolipoprotein B (ApoB and ApoA in CI group were detected. Results The frequency of Val allele (78.45% and Val/Valgenotype (61.33% in CI was significantly higher than that in the control group (68.24% and 45.95%, P 0.05 than that in the control group. The serum levels of glucose, TC, TG, LDL-C, HDL-C, ApoB, ApoA and the frequency of hypertension had no difference between Val/Val genotype and Val/Met + Met/Met genotypes ( P > 0.05, for all. Conclusion The frequencies of Val allele and Val/Val genotype can be considered as genetic risk factors of male CI patients. The effect of COMT on CI is not related to blood pressure, serum lipid and glucose.

  20. The relationship between childhood abuse and dissociation. Is it influenced by catechol-O-methyltransferase (COMT) activity?

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    Savitz, Jonathan B; van der Merwe, Lize; Newman, Timothy K; Solms, Mark; Stein, Dan J; Ramesar, Rajkumar S

    2008-03-01

    Dissociation is a failure of perceptual, memorial and emotional integration that is associated with a variety of psychiatric disorders. Dissociative processes are usually attributed to the sequelae of childhood trauma although there are data to suggest that genetic influences are also important. Bipolar disorder (BD), a condition with a strong genetic basis, has also been associated with early psychological trauma. Since childhood trauma is a risk factor for both BD and dissociation, we tested for potential gene-childhood abuse interactions on dissociation in a pilot sample of BD probands and their affected and unaffected relatives (n=178). Dissociation was measured with the Dissociative Experiences Scale (DES II) and childhood maltreatment with the Childhood Trauma Questionnaire (CTQ). The BD and recurrent unipolar depression (MDE-R) groups showed higher levels of self-reported abuse and dissociation than their unaffected relatives. The low-activity Met allele of the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene was associated with lower levels of self-reported dissociation. Further, the functional catechol-O-methyltransferase (COMT) Val158Met polymorphism interacted significantly with total CTQ abuse scores to impact perceived dissociation. The Val/Val genotype was associated with increasing levels of dissociation in participants exposed to higher levels of childhood trauma. The opposite was observed in people with Met/Met genotypes who displayed decreased dissociation with increasing self-reported childhood trauma. The current findings support the involvement of the COMT Val158Met polymorphism in mediating the relationship between trauma and psychopathology.

  1. The MAOA and COMT Gene Polymorphisms in Patients with Schizophrenia Committed Homicide

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    V.A. Soldatkin

    2014-12-01

    Full Text Available Numerous studies have indicated that aggression and homicide are more frequent among people with schizophrenia than in the general population. There is considerable evidence that schizophrenia involves a dysbalance between subcortical and cortical dopaminergic systems. The major pathways for catecholamine degradation are oxidative deamination through the action of monoamine oxidase A (MAOA and by methylation through the action of catechol-O-methyltransferase (COMT. Activity of both enzymes is encoded by the corresponding genes—MAOA and COMT. The aim of our study was to analyze the association between the COMT-Val158Met and MAOA-uVNTR polymorphisms and the risk of committing homicide by patients with schizophrenia. Methods: The study included 50 Caucasian male patients with paranoid schizophrenia (PS. All patients were divided into two groups: Group 1 consisted of 26 PS patients who have committed homicide; Group 2 consisted of 24 PS patients who did not have a history of socially violent behavior. The control group comprised 23 apparently healthy Caucasian men of the same age. All patients underwent clinical-psychopathological and clinical-anamnestic examinations. Molecular genetic studies were performed in the Shared Research Facility Center "High Technologies" at SFedU. Results: Our study revealed no direct correlation between the COMT-Val158Met and MAOA-uVNTR polymorphisms and risk of committing homicide by patients with schizophrenia. At the same time, we detected an association between high-activity gene variants, viz., the MAOA-4R allele and the COMT-158Met/158Met genotype, and the schizoid and unstable premorbid accentuation in patients who had committed murder, whereas the schizoid and unstable accentuation correlated with homicide behavior in patients with schizophrenia. Conclusion: The obtained findings suggest that genetic variation affects the homicidal behavior indirectly, through the various types of premorbid accentuation and

  2. Sex Differences in COMT Polymorphism Effects on Prefrontal Inhibitory Control in Adolescence

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    White, Thomas P; Loth, Eva; Rubia, Katya; Krabbendam, Lydia; Whelan, Robert; Banaschewski, Tobias; Barker, Gareth J; Bokde, Arun LW; Büchel, Christian; Conrod, Patricia; Fauth-Bühler, Mira; Flor, Herta; Frouin, Vincent; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Ittermann, Bernd; Lawrence, Claire; Mann, Karl; Paillère, Marie-Laure; Nees, Frauke; Paus, Tomas; Pausova, Zdenka; Rietschel, Marcella; Robbins, Trevor; Smolka, Michael N; Shergill, Sukhwinder S; Schumann, Gunter

    2014-01-01

    Catecholamine-0-methyl-transferase (COMT) gene variation effects on prefrontal blood oxygenation-level-dependent (BOLD) activation are robust; however, despite observations that COMT is estrogenically catabolized, sex differences in its prefrontal repercussions remain unclear. Here, in a large sample of healthy adolescents stratified by sex and Val158Met genotype (n=1133), we examine BOLD responses during performance of the stop-signal task in right-hemispheric prefrontal regions fundamental to inhibitory control. A significant sex-by-genotype interaction was observed in pre-SMA during successful-inhibition trials and in both pre-SMA and inferior frontal cortex during failed-inhibition trials with Val homozygotes displaying elevated activation compared with other genotypes in males but not in females. BOLD activation in the same regions significantly mediated the relationship between COMT genotype and inhibitory proficiency as indexed by stop-signal reaction time in males alone. These sexually dimorphic effects of COMT on inhibitory brain activation have important implications for our understanding of the contrasting patterns of prefrontally governed psychopathology observed in males and females. PMID:24820538

  3. COMT polymorphism modulates the resting-state EEG alpha oscillatory response to acute nicotine in male non-smokers.

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    Bowers, H; Smith, D; de la Salle, S; Choueiry, J; Impey, D; Philippe, T; Dort, H; Millar, A; Daigle, M; Albert, P R; Beaudoin, A; Knott, V

    2015-07-01

    Performance improvements in cognitive tasks requiring executive functions are evident with nicotinic acetylcholine receptor (nAChR) agonists, and activation of the underlying neural circuitry supporting these cognitive effects is thought to involve dopamine neurotransmission. As individual difference in response to nicotine may be related to a functional polymorphism in the gene encoding catechol-O-methyltransferase (COMT), an enzyme that strongly influences cortical dopamine metabolism, this study examined the modulatory effects of the COMT Val158Met polymorphism on the neural response to acute nicotine as measured with resting-state electroencephalographic (EEG) oscillations. In a sample of 62 healthy non-smoking adult males, a single dose (6 mg) of nicotine gum administered in a randomized, double-blind, placebo-controlled design was shown to affect α oscillatory activity, increasing power of upper α oscillations in frontocentral regions of Met/Met homozygotes and in parietal/occipital regions of Val/Met heterozygotes. Peak α frequency was also found to be faster with nicotine (vs. placebo) treatment in Val/Met heterozygotes, who exhibited a slower α frequency compared to Val/Val homozygotes. The data tentatively suggest that interindividual differences in brain α oscillations and their response to nicotinic agonist treatment are influenced by genetic mechanisms involving COMT. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  4. Attention Deficit Hyperactivity Disorder comorbid oppositional defiant disorder and its predominately inattentive type: evidence for an association with COMT but not MAOA in a Chinese sample

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    Wang Yu-Feng

    2009-02-01

    Full Text Available Abstract Background There are three childhood disruptive behavior disorders (DBDs, attention deficit hyperactivity disorder (ADHD, oppositional defiant disorder (ODD, and conduct disorder (CD. The most common comorbid disorder in ADHD is ODD. DSM-IV describes three ADHD subtypes: predominantly inattentive type (ADHD-IA, predominantly hyperactive-impulsive type (ADHD-HI, and combined type (ADHD-C. Prior work suggests that specific candidate genes are associated with specific subtypes of ADHD in China. Our previous association studies between ADHD and functional polymorphisms of COMT and MAOA, consistently showed the low transcriptional activity alleles were preferentially transmitted to ADHD-IA boys. Thus, the goal of the present study is to test the hypothesis that COMT Val158Met and MAOA-uVNTR jointly contribute to the ODD phenotype among Chinese ADHD boys. Methods 171 Chinese boys between 6 and 17.5 years old (mean = 10.3, SD = 2.6 with complete COMT val158met and MAOA-uVNTR genotyping information were studied. We used logistic regression with genotypes as independent variables and the binary phenotype as the dependent variable. We used p Results Our results highlight the potential etiologic role of COMT in the ADHD with comorbid ODD and its predominately inattentive type in male Chinese subjects. ADHD with comorbid ODD was associated with homozygosity of the high-activity Val allele, while the predominantly inattentive ADHD subtype was associated with the low-activity Met allele. We found no evidence of association between the MAOA-uVNTR variant and ADHD with comorbid ODD or the ADHD-IA subtype. Conclusion Our study of attention deficit hyperactivity disorder comorbid oppositional defiant disorder and its predominately inattentive type highlights the potential etiologic role of COMT for ADHD children in China. But we failed to observe an interaction between COMT and MAOA, which suggests that epistasis between COMT and MAOA genes does not

  5. Magnified effects of the COMT gene on white-matter microstructure in very old age.

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    Papenberg, Goran; Lövdén, Martin; Laukka, Erika J; Kalpouzos, Grégoria; Keller, Lina; Graff, Caroline; Köhncke, Ylva; Li, Tie-Qiang; Fratiglioni, Laura; Bäckman, Lars

    2015-09-01

    Genetic factors may partly account for between-person differences in brain integrity in old age. Evidence from human and animal studies suggests that the dopaminergic system is implicated in the modulation of white-matter integrity. We investigated whether a genetic variation in the Catechol-O-Methyltransferase (COMT) Val158Met polymorphism, which influences dopamine availability in prefrontal cortex, contributes to interindividual differences in white-matter microstructure, as measured with diffusion-tensor imaging. In a sample of older adults from a population-based study (60-87 years; n = 238), we found that the COMT polymorphism affects white-matter microstructure, indexed by fractional anisotropy and mean diffusivity, of several white-matter tracts in the oldest age group (81-87 years), although there were no reliable associations between COMT and white-matter microstructure in the two younger age groups (60-66 and 72-78 years). These findings extend previous observations of magnified genetic effects on cognition in old age to white-matter integrity.

  6. The study of the association between COMT polymorphisms and methylphenidate response in the treat-ment of attention deficit hyperactivity disorder%注意缺陷多动障碍COMT基因多态性与哌甲酯疗效研究

    Institute of Scientific and Technical Information of China (English)

    陈敏; 李海梅; 王玉凤; 杨莉

    2014-01-01

    Objective To explore the impacts of catechol-O-Methyltransferase (COMT) gene polymorphisms on the outcomes of methylphenidate treatment for attention deficit hyperactivity disorder (ADHD) in children. Methods One hundred seventy-seven ADHD children of Chinese Han descent received open-labelled dose titration with methylpheni⁃date to achieve optimal response in 2~4 weeks. The behavior changes were evaluated by using ADHD diagnostic scale (parent version) before and after treatment. COMT gene rs4680 (Val158Met) and rs165599 were genotyped using fluores⁃cent real-time PCR. The genotype distribution and treatment outcomes including remission, response and non-response were analyzed. Results The treatment response differed significantly among patients with different genotypes of rs4680 (P0.05). Conclu⁃sion COMT gene rs4680 (Val158Met) polymorphism is associated with methylphenidate response in a Han Chinese popu⁃lation. Patients with G allele is more likely to benefit from methylphenidate treatment in comparison with A/A genotype.%目的:探讨儿茶酚-O-甲基转移酶(catechol-O-Methyltransferase,COMT)基因多态性对注意缺陷多动障碍(attention deficit hyperactivity disorder,ADHD)儿童服用哌甲酯治疗效果的影响。方法对177例汉族ADHD患儿进行2~4周的哌甲酯开放剂量滴定,获得最佳治疗反应。在治疗前后使用ADHD诊断量表(父母版)对患儿行为变化进行定量评估,并将疗效分为缓解、有效和无效。检测COMT基因rs4680(Val158Met)和rs165599多态性,比较不同基因型患儿的疗效。结果 rs4680不同基因型患儿治疗效果的差异有统计学意义(P0.05)。结论COMT基因rs4680(Val158Met)多态性与哌甲酯治疗反应存在关联,rs4680的G等位基因携带者治疗反应优于A/A基因型者。

  7. Clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy": the influence of gender and genetics (CYP2D6, COMT, 5-HTT.

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    Ricardo Pardo-Lozano

    Full Text Available The synthetic psychostimulant MDMA (± 3,4-methylenedioxymethamphetamine, ecstasy acts as an indirect serotonin, dopamine, and norepinephrine agonist and as a mechanism-based inhibitor of the cytochrome P-450 2D6 (CYP2D6. It has been suggested that women are more sensitive to MDMA effects than men but no clinical experimental studies have satisfactorily evaluated the factors contributing to such observations. There are no studies evaluating the influence of genetic polymorphism on the pharmacokinetics (CYP2D6; catechol-O-methyltransferase, COMT and pharmacological effects of MDMA (serotonin transporter, 5-HTT; COMT. This clinical study was designed to evaluate the pharmacokinetics and physiological and subjective effects of MDMA considering gender and the genetic polymorphisms of CYP2D6, COMT, and 5-HTT. A total of 27 (12 women healthy, recreational users of ecstasy were included (all extensive metabolizers for CYP2D6. A single oral weight-adjusted dose of MDMA was administered (1.4 mg/kg, range 75-100 mg which was similar to recreational doses. None of the women were taking oral contraceptives and the experimental session was performed during the early follicular phase of their menstrual cycle. Principal findings show that subjects reached similar MDMA plasma concentrations, and experienced similar positive effects, irrespective of gender or CYP2D6 (not taking into consideration poor or ultra-rapid metabolizers or COMT genotypes. However, HMMA plasma concentrations were linked to CYP2D6 genotype (higher with two functional alleles. Female subjects displayed more intense physiological (heart rate, and oral temperature and negative effects (dizziness, sedation, depression, and psychotic symptoms. Genotypes of COMT val158met or 5-HTTLPR with high functionality (val/val or l/* determined greater cardiovascular effects, and with low functionality (met/* or s/s negative subjective effects (dizziness, anxiety, sedation. In conclusion, the contribution

  8. The COMT Val/Met polymorphism is associated with reading-related skills and consistent patterns of functional neural activation.

    Science.gov (United States)

    Landi, Nicole; Frost, Stephen J; Mencl, W Einar; Preston, Jonathan L; Jacobsen, Leslie K; Lee, Maria; Yrigollen, Carolyn; Pugh, Kenneth R; Grigorenko, Elena L

    2013-01-01

    In both children and adults there is large variability in reading skill, with approximately 5-10% of individuals characterized as having reading disability; these individuals struggle to learn to read despite adequate intelligence and opportunity. Although it is well established that a substantial portion of this variability is attributed to the genetic differences between individuals, specifics of the connections between reading and the genome are not understood. This article presents data that suggest that variation in the COMT gene, which has previously been associated with variation in higher-order cognition, is associated with reading and reading-related skills, at the level of both brain and behavior. In particular, we found that the COMT Val/Met polymorphism at rs4680, which results in the substitution of the ancestral Valine (Val) by Methionine (Met), was associated with better performance on a number of critical reading measures and with patterns of functional neural activation that have been linked to better readers. We argue that this polymorphism, known for its broad effects on cognition, may modulate (likely through frontal lobe function) reading skill. © 2012 Blackwell Publishing Ltd.

  9. Adipose tissue PCB levels and CYP1B1 and COMT genotypes in relation to breast cancer risk in postmenopausal Danish women.

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    Bräuner, Elvira V; Loft, Steffen; Wellejus, Anja; Autrup, Herman; Tjønneland, Anne; Raaschou-Nielsen, Ole

    2014-01-01

    Exposure to PCBs may be an etiologic factor for breast cancer. The cytochrome P450 1B1 (CYP1B1) and catechol-O-methyltransferase (COMT) enzymes are involved in estrogen metabolism and PCB metabolism, both of which may relate to breast cancer susceptibility. Polymorphisms in genes regulating these enzymes control efficiency. Our objective was to assess whether CYP1B1 and COMT gene polymorphisms modulate the effect of PCBs in breast cancer risk, among postmenopausal Danish women. Neither CYP1B1 Leu432Val polymorphisms nor adipose tissue PCBs were independently associated with breast cancer risk. When assessing the independent effect of the COMT Val158Met polymorphism, we observed reduced risk for breast cancer amongst hormone replacement therapy using women who were homozygous carriers of the variant allele compared with those carrying the wild-type variant (RR = 0.41; 95% CI: 0.29-0.89). We found no statistically significant interactions between any of the PCB groups and CYP1B1 or COMT polymorphisms on the risk of breast cancer.

  10. Genetic variation in the Catechol-O-Methyltransferase (COMT gene and morphine requirements in cancer patients with pain

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    Kaasa Stein

    2008-12-01

    Full Text Available Abstract Background Genetic variation contributes to differences in pain sensitivity and response to different analgesics. Catecholamines are involved in the modulation of pain and are partly metabolized by the catechol-O-methyltransferase (COMT enzyme. Genetic variability in the COMT gene may therefore contribute to differences in pain sensitivity and response to analgesics. It is shown that a polymorphism in the COMT gene, Rs4680 (Val158Met, influence pain sensitivity in human experimental pain and the efficacy for morphine in cancer pain treatment. In this study we wanted to investigate if variability in other regions in the COMT gene also contributes to interindividual variability in morphine efficacy. Results We genotyped 11 single nucleotide polymorphisms (SNPs throughout the COMT gene, and constructed haplotypes from these 11 SNPs, which were in Hardy-Weinberg equilibrium. We compared both genotypes and haplotypes against pharmacological, demographical and patient symptoms measurements in a Caucasian cancer patient cohort (n = 197 receiving oral morphine treatment for cancer pain. There were two frequent haplotypes (34.5% and 17.8% in our cohort. Multivariate analyses showed that patients carrying the most frequent haplotype (34.5% needed lower morphine doses than patients not carrying the haplotype, with a reduction factor of 0.71 (p = 0.005. On the allele level, carriers of alleles for six of the SNPs show weak associations in respect to morphine dose and the alleles associated with the lowest morphine doses constitute part of the most frequent haplotype. Conclusion This study suggests that genetic variability in the COMT gene influence the efficacy of morphine in cancer patients with pain, and that increased understanding of this variability is reached by expanding from analyses of single SNPs to haplotype construction and analyses.

  11. Catechol-O-methyltransferase (COMT Genotype Affects Age-Related Changes in Plasticity in Working Memory: A Pilot Study

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    Stephan Heinzel

    2014-01-01

    Full Text Available Objectives. Recent work suggests that a genetic variation associated with increased dopamine metabolism in the prefrontal cortex (catechol-O-methyltransferase Val158Met; COMT amplifies age-related changes in working memory performance. Research on younger adults indicates that the influence of dopamine-related genetic polymorphisms on working memory performance increases when testing the cognitive limits through training. To date, this has not been studied in older adults. Method. Here we investigate the effect of COMT genotype on plasticity in working memory in a sample of 14 younger (aged 24–30 years and 25 older (aged 60–75 years healthy adults. Participants underwent adaptive training in the n-back working memory task over 12 sessions under increasing difficulty conditions. Results. Both younger and older adults exhibited sizeable behavioral plasticity through training (P<.001, which was larger in younger as compared to older adults (P<.001. Age-related differences were qualified by an interaction with COMT genotype (P<.001, and this interaction was due to decreased behavioral plasticity in older adults carrying the Val/Val genotype, while there was no effect of genotype in younger adults. Discussion. Our findings indicate that age-related changes in plasticity in working memory are critically affected by genetic variation in prefrontal dopamine metabolism.

  12. Catechol-O-methyltransferase (COMT) Genotype Affects Age-Related Changes in Plasticity in Working Memory: A Pilot Study

    Science.gov (United States)

    Riemer, Thomas G.; Schulte, Stefanie; Onken, Johanna; Heinz, Andreas; Rapp, Michael A.

    2014-01-01

    Objectives. Recent work suggests that a genetic variation associated with increased dopamine metabolism in the prefrontal cortex (catechol-O-methyltransferase Val158Met; COMT) amplifies age-related changes in working memory performance. Research on younger adults indicates that the influence of dopamine-related genetic polymorphisms on working memory performance increases when testing the cognitive limits through training. To date, this has not been studied in older adults. Method. Here we investigate the effect of COMT genotype on plasticity in working memory in a sample of 14 younger (aged 24–30 years) and 25 older (aged 60–75 years) healthy adults. Participants underwent adaptive training in the n-back working memory task over 12 sessions under increasing difficulty conditions. Results. Both younger and older adults exhibited sizeable behavioral plasticity through training (P < .001), which was larger in younger as compared to older adults (P < .001). Age-related differences were qualified by an interaction with COMT genotype (P < .001), and this interaction was due to decreased behavioral plasticity in older adults carrying the Val/Val genotype, while there was no effect of genotype in younger adults. Discussion. Our findings indicate that age-related changes in plasticity in working memory are critically affected by genetic variation in prefrontal dopamine metabolism. PMID:24772423

  13. Inhibition of catechol-O-methyl transferase (COMT) by tolcapone restores reductions in microtubule-associated protein 2 (MAP2) and synaptophysin (SYP) following exposure of neuronal cells to neurotropic HIV.

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    Lee, Ting Ting; Chana, Gursharan; Gorry, Paul R; Ellett, Anne; Bousman, Chad A; Churchill, Melissa J; Gray, Lachlan R; Everall, Ian P

    2015-10-01

    This investigation aimed to assess whether inhibition of cathecol-O-methyl transferase (COMT) by tolcapone could provide neuroprotection against HIV-associated neurodegenerative effects. This study was conducted based on a previous work, which showed that a single nucleotide polymorphism (SNP) at position 158 (val158met) in COMT, resulted in 40 % lower COMT activity. Importantly, this reduction confers a protective effect against HIV-associated neurocognitive disorders (HAND), which have been linked to HIV-associated brain changes. SH-SY5Y-differentiated neurons were exposed to macrophage-propagated HIV (neurotropic MACS2-Br strain) in the presence or absence of tolcapone for 6 days. RNA was extracted, and qPCR was performed using Qiagen RT2 custom array consisting of genes for neuronal and synaptic integrity, COMT and pro-inflammatory markers. Immunofluorescence was conducted to validate the gene expression changes at the protein level. Our findings demonstrated that HIV significantly increased the messenger RNA (mRNA) expression of COMT while reducing the expression of microtubule-associated protein 2 (MAP2) (p = 0.0015) and synaptophysin (SYP) (p = 0.012) compared to control. A concomitant exposure of tolcapone ameliorated the perturbed expression of MAP2 (p = 0.009) and COMT (p = 0.024) associated with HIV. Immunofluorescence revealed a trend reduction of SYP and MAP2 with exposure to HIV and that concomitant exposure of tolcapone increased SYP (p = 0.016) compared to HIV alone. Our findings demonstrated in vitro that inhibition of COMT can ameliorate HIV-associated neurodegenerative changes that resulted in the decreased expression of the structural and synaptic components MAP2 and SYP. As HIV-associated dendritic and synaptic damage are contributors to HAND, inhibition of COMT may represent a potential strategy for attenuating or preventing some of the symptoms of HAND.

  14. Inhibition of Catechol-O-methyl Transferase (COMT) by Tolcapone Restores Reductions in Microtubule-associated Protein 2 (MAP2) and Synaptophysin (SYP) Following Exposure of Neuronal Cells to Neurotropic HIV

    Science.gov (United States)

    Lee, Ting Ting; Chana, Gursharan; Gorry, Paul R.; Ellett, Anne; Bousman, Chad A.; Churchill, Melissa J.; Gray, Lachlan R.; Everall, Ian P.

    2015-01-01

    This investigation aimed to assess whether inhibition of cathecol-O-methyl transferase (COMT) by Tolcapone could provide neuroprotection against HIV-associated neurodegenerative effects. This study was conducted based on previous work, which showed that a single nucleotide polymorphism (SNP) at position 158 (val158met) in COMT, resulted in 40% lower COMT activity. Importantly, this reduction confers a protective effect against HIV-associated neurocognitive disorders (HAND), which have been linked to HIV-associated brain changes. SH-SY5Y differentiated neurons were exposed to macrophage-propagated HIV (neurotropic MACS2-Br strain) in the presence or absence of Tolcapone for 6 days. RNA was extracted and qPCR was performed using Qiagen RT2-custom-array consisting of genes for neuronal and synaptic integrity, COMT and pro-inflammatory markers. Immunofluorescence was conducted to validate the gene expression changes at the protein level. Our findings demonstrated that HIV significantly increased the mRNA expression of COMT while reduced the expression of microtubule-associated protein 2 (MAP2) (p=0.0015) and synaptophysin (SYP) (p=0.012) compared to control. A concomitant exposure of Tolcapone ameliorated the perturbed expression of MAP2 (p=0.009) and COMT (p=0.024) associated with HIV. Immunofluorescence revealed a trend reduction of SYP and MAP2 with exposure to HIV, and that concomitant exposure of Tolcapone increased SYP (p=0.016) compared to HIV alone. Our findings demonstrated in vitro that inhibition of COMT can ameliorate HIV-associated neurodegenerative changes that resulted in the decreased expression of the structural and synaptic components MAP2 and SYP. As HIV-associated dendritic and synaptic damage are contributors to HAND, inhibition of COMT may represent a potential strategy for attenuating or preventing some of the symptoms of HAND. PMID:26037113

  15. Evidence for a common biological basis of the Absorption trait, hallucinogen effects, and positive symptoms: epistasis between 5-HT2a and COMT polymorphisms.

    Science.gov (United States)

    Ott, Ulrich; Reuter, Martin; Hennig, Juergen; Vaitl, Dieter

    2005-08-05

    Absorption represents a disposition to experience altered states of consciousness characterized by intensively focused attention. It is correlated with hypnotic susceptibility and includes phenomena ranging from vivid perceptions and imaginations to mystical experiences. Based on the assumption that drug-induced and naturally occurring mystical experiences share common neural mechanisms, we hypothesized that Absorption is influenced by the T102C polymorphism affecting the 5-HT2a receptor, which is known to be an important target site of hallucinogens like LSD. Based on the pivotal role ascribed to the prefrontal executive control network for absorbed attention and positive symptoms in schizophrenia, it was further hypothesized that Absorption is associated with the VAL158MET polymorphism of the catechol-O-methyltransferase (COMT) gene affecting the dopaminergic neurotransmitter system. The Tellegen Absorption Scale was administered to 336 subjects (95 male, 241 female). Statistical analysis revealed that the group with the T/T genotype of the T102C polymorphism, implying a stronger binding potential of the 5-HT2a receptor, indeed had significantly higher Absorption scores (F = 10.00, P = 0.002), while no main effect was found for the COMT polymorphism. However, the interaction between T102C and COMT genotypes yielded significance (F = 3.89; P = 0.049), underlining the known functional interaction between the 5-HT and the dopaminergic system. These findings point to biological foundations of the personality trait of Absorption. (c) 2005 Wiley-Liss, Inc.

  16. Monoamine Oxidase A (MAOA) and Catechol-O-Methyltransferase (COMT) Gene Polymorphisms Interact with Maternal Parenting in Association with Adolescent Reactive Aggression but not Proactive Aggression: Evidence of Differential Susceptibility.

    Science.gov (United States)

    Zhang, Wenxin; Cao, Cong; Wang, Meiping; Ji, Linqin; Cao, Yanmiao

    2016-04-01

    To date, whether and how gene-environment (G × E) interactions operate differently across distinct subtypes of aggression remains untested. More recently, in contrast with the diathesis-stress hypothesis, an alternative hypothesis of differential susceptibility proposes that individuals could be differentially susceptible to environments depending on their genotypes in a "for better and for worse" manner. The current study examined interactions between monoamine oxidase A (MAOA) T941G and catechol-O-methyltransferase (COMT) Val158Met polymorphisms with maternal parenting on two types of aggression: reactive and proactive. Moreover, whether these potential G × E interactions would be consistent with the diathesis-stress versus the differential susceptibility hypothesis was tested. Within the sample of 1399 Chinese Han adolescents (47.2 % girls, M age = 12.32 years, SD = 0.50), MAOA and COMT genes both interacted with positive parenting in their associations with reactive but not proactive aggression. Adolescents with T alleles/TT homozygotes of MAOA gene or Met alleles of COMT gene exhibited more reactive aggression when exposed to low positive parenting, but less reactive aggression when exposed to high positive parenting. These findings provide the first evidence for distinct G × E interaction effects on reactive versus proactive aggression and lend further support for the differential susceptibility hypothesis.

  17. COMT and prenatal maternal smoking in associations with conduct problems and crime: the Pelotas 1993 birth cohort study.

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    Salatino-Oliveira, Angélica; Murray, Joseph; Kieling, Christian; Genro, Júlia Pasqualini; Polanczyk, Guilherme; Anselmi, Luciana; Wehrmeister, Fernando; de Barros, Fernando C; Menezes, Ana Maria Baptista; Rohde, Luis Augusto; Hutz, Mara Helena

    2016-07-18

    Conduct problems in childhood and adolescence are significant precursors of crime and violence in young adulthood. The purpose of the current study is to test the interaction between prenatal maternal smoking and COMT Val(158)Met in conduct problems and crime in the 1993 Pelotas Birth Cohort Study. Conduct problems were assessed through the parent version of the Strengths and Difficulties Questionnaire at ages 11 and 15 years. A translated version of a confidential self-report questionnaire was used to collect criminal data at 18 years of age. Negative binomial regression analyses showed an association between prenatal maternal smoking and SDQ conduct problem scores (IRR = 1.24; 95% CI: 1.14-1.34; p gene in predicting conduct problems. Very similar results were obtained using the 15 years conduct scores and crime measure at age 18. Prenatal maternal smoking was associated with crime (IRR = 1.28; 95% CI: 1.09-1.48; p = 0.002) but neither COMT genotypes nor the possible interaction between gene and maternal smoking were significantly associated with crime. Replications of GxE findings across different social contexts are critical for testing the robustness of findings.

  18. The brain-derived neurotrophic factor (BDNF) val66met polymorphism differentially affects performance on subscales of the Wechsler Memory Scale - Third Edition (WMS-III).

    Science.gov (United States)

    Lamb, Yvette N; Thompson, Christopher S; McKay, Nicole S; Waldie, Karen E; Kirk, Ian J

    2015-01-01

    Single nucleotide polymorphisms in the brain-derived neurotrophic factor (BDNF) gene and the catechol-O-methyltransferase (COMT) gene influence brain structure and function, as well as cognitive abilities. They are most influential in the hippocampus and prefrontal cortex (PFC), respectively. Recall and recognition are forms of memory proposed to have different neural substrates, with recall having a greater dependence on the PFC and hippocampus. This study aimed to determine whether the BDNF val(66)met or COMT val(158)met polymorphisms differentially affect recall and recognition, and whether these polymorphisms interact. A sample of 100 healthy adults was assessed on recall and familiarity-based recognition using the Faces and Family Pictures subscales of the Wechsler Memory Scale - Third Edition (WMS-III). COMT genotype did not affect performance on either task. The BDNF polymorphism (i.e., met carriers relative to val homozygotes) was associated with poorer recall ability, while not influencing recognition. Combining subscale scores in memory tests such as the WMS might obscure gene effects. Our results demonstrate the importance of distinguishing between recall and familiarity-based recognition in neurogenetics research.

  19. The brain-derived neurotrophic factor (BDNF val66met polymorphism differentially affects performance on subscales of the Wechsler memory scale – third edition (WMS-III

    Directory of Open Access Journals (Sweden)

    Yvette Nicole Lamb

    2015-08-01

    Full Text Available Single nucleotide polymorphisms in the brain-derived neurotrophic factor (BDNF gene and the catechol-O-methyltransferase (COMT gene influence brain structure and function, as well as cognitive abilities. They are most influential in the hippocampus and prefrontal cortex (PFC, respectively. Recall and recognition are forms of memory proposed to have different neural substrates, with recall having a greater dependence on the PFC and hippocampus. This study aimed to determine whether the BDNF val66met or COMT val158met polymorphisms differentially affect recall and recognition, and whether these polymorphisms interact. A sample of 100 healthy adults was assessed on recall and familiarity-based recognition using the Faces and Family Pictures subscales of the Wechsler Memory Scale – Third Edition (WMS-III. COMT genotype did not affect performance on either task. The BDNF polymorphism (i.e. met carriers relative to val homozygotes was associated with poorer recall ability, while not influencing recognition. Combining subscale scores in memory tests such as the WMS might obscure gene effects. Our results demonstrate the importance of distinguishing between recall and familiarity-based recognition in neurogenetics research.

  20. Dopamine metabolism in adults with 22q11 deletion syndrome, with and without schizophrenia--relationship with COMT Val¹⁰⁸/¹⁵⁸Met polymorphism, gender and symptomatology.

    Science.gov (United States)

    Boot, Erik; Booij, Jan; Abeling, Nico; Meijer, Julia; da Silva Alves, Fabiana; Zinkstok, Janneke; Baas, Frank; Linszen, Don; van Amelsvoort, Thérèse

    2011-07-01

    22q11 Deletion syndrome (22q11DS) is a major risk factor for schizophrenia. In addition, both conditions are associated with alterations of the dopaminergic system. The catechol-O-methyltransferase (COMT) gene, located within the deleted region, encodes for the enzyme COMT that is important for degradation of catecholamines, including dopamine (DA). COMT activity is sexually dimorphic and its gene contains a functional polymorphism, Val¹⁰⁸/¹⁵⁸ Met; the Met allele is associated with lower enzyme activity. We report the first controlled catecholamine study in 22q11DS-related schizophrenia. Twelve adults with 22q11DS with schizophrenia (SCZ+) and 22 adults with 22q11DS without schizophrenia (SCZ-) were genotyped for the COMT Val¹⁰⁸/¹⁵⁸ Met genotype. We assessed dopaminergic markers in urine and plasma. We also correlated these markers with scores on the Positive and Negative Symptom Scale (PANSS). Contrary to our expectations, we found SCZ+ subjects to be more often Val hemizygous and SCZ- subjects more often Met hemizygous. Significant COMT cross gender interactions were found on dopaminergic markers. In SCZ+ subjects there was a negative correlation between prolactin levels and scores on the general psychopathology subscale of the PANSS scores. These findings suggest intriguing, but complex, interactions of the COMT Val¹⁰⁸/¹⁵⁸ Met polymorphism, gender and additional factors on DA metabolism, and its relationship with schizophrenia.

  1. COMT Val[superscript 108/158] Met Gene Variant, Birth Weight, and Conduct Disorder in Children with ADHD

    Science.gov (United States)

    Sengupta, Sarojini M.; Grizenko, Natalie; Schmitz, Norbert; Schwartz, George; Amor, Leila Ben; Bellingham, Johanne; de Guzman, Rosherrie; Polotskaia, Anna; Stepanian, Marina Ter; Thakur, Geeta; Joober, Ridha

    2006-01-01

    Objective: In a recent study, Thapar and colleagues reported that COMT "gene variant and birth weight predict early-onset antisocial behavior in children" with attention-deficit/hyperactivity disorder. We have attempted to replicate these findings in a group of ADHD children using a similar research design. Method: Children (n = 191)…

  2. The role of COMT polymorphism in risperidone-induced hyperprolactinemia in female ;schizophrenia patients%儿茶酚氧位甲基转移酶基因多态性对利培酮治疗女性精神分裂症患者所致高泌乳素血症的影响

    Institute of Scientific and Technical Information of China (English)

    陈钰; 钱程; 戢秋明; 高树贵; 周东升

    2014-01-01

    Objective To study the association between COMT polymorphism and the hyperprolactinemia of Risperidone in female schizophrenia patients. Methods A total of 62 Chinese Han schizophrenic patients that examined by trained psychiatrists using the Chinese Classification of Mental Disorders (CCMD-3) criteria were recruited in this retrospective study. A microparticle enzyme immunoassay was used for measuring the serum prolactin levels at the beginning of the study and the time of receiving risperidone treatment on the 8th week. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for COMT genotypes determined. Results There was no significant association between the COMT Val158Met polymorphism and demographic characteristics of the patients in this study. The prolactin level increases significantly after risperidone treatment (P<0.001). However, the Val/Val genotype of the patients showed the lowest prolactin level in all subjects (P=0.003). Conclusion The COMT Val158/108Met polymorphism may be a potential biomarker with predictive value in Risperidone-induced hyperprolactinemia in female schizophrenia patients.%目的:探讨儿茶酚氧位甲基转移酶(COMT)的基因多态性与利培酮在女性精神分裂症(SCZ)患者中所致的泌乳素升高之间的相关性。方法按照符合美国精神病学会的精神障碍诊断和统计手册第四修订版(DSM-Ⅳ)诊断标准,收集湖北省武汉市武东医院和宁波市康宁医院62例中国汉族女性SCZ患者作为研究对象,对照组选取社区汉族女性健康志愿者,共完成65人。两组民族、性别相同,年龄、文化程度差异无统计学意义。利培酮药物治疗前与治疗8周后分别抽取其外周血液样本,采用微粒酶免疫分析法对用药前后的泌乳素含量进行测定,利用聚合酶链式反应-限制性片段长度多态分析(PCR-RFLP)技术对患者外周血所取提取的基因

  3. The Flexible Mind Is Associated with the Catechol-O-Methyltransferase (COMT) Val[superscript 158]Met Polymorphism: Evidence for a Role of Dopamine in the Control of Task-Switching

    Science.gov (United States)

    Colzato, Lorenza S.; Waszak, Florian; Nieuwenhuis, Sander; Posthuma, Danielle; Hommel, Bernhard

    2010-01-01

    Genetic variability related to the catechol-O-methyltransferase (COMT) gene Val[superscript 128]Met polymorphism) has received increasing attention as a possible modulator of cognitive control functions. Recent evidence suggests that the Val[superscript 128]Met genotype may differentially affect cognitive stability and flexibility, in such a way…

  4. Supraphysiological hormonal status, anxiety disorders, and COMT Val/Val genotype are associated with reduced sensorimotor gating in women.

    Science.gov (United States)

    Comasco, Erika; Hellgren, Charlotte; Olivier, Jocelien; Skalkidou, Alkistis; Sundström Poromaa, Inger

    2015-10-01

    Pregnancy is a period characterized by a supraphysiological hormonal status, and greater anxiety proneness, which can lead to peripartum affective symptoms with dramatic consequences not only for the woman but also for the child. Clinical psychiatry is heavily hampered by the paucity of objective and biology-based intermediate phenotypes. Prepulse inhibition (PPI) of the startle response, a neurophysiological measure of sensorimotor gating, has been poorly investigated in relation to anxiety and in pregnant women. In the present study, the PPI of healthy non-pregnant women (n = 82) and late pregnant women (n = 217) was investigated. Age, BMI, depression and anxiety symptoms, tobacco use, and antidepressant medication were considered. We investigated and provided evidence of lower PPI: (i) in healthy pregnant women compared to healthy non-pregnant controls, (ii) in pregnant women with anxiety disorders compared to healthy pregnant women, (iii) in pregnant women with anxiety disorders using SSRI compared to un-medicated pregnant women with anxiety disorders, and (iv) in healthy pregnant women carrying the COMT Val158Met Val/Val genotype compared to Met carriers. Altogether, a reduced sensorimotor gating as an effect of supraphysiological hormonal status, anxiety disorders, SSRIs, and catecholaminergic genotype, implicate the putative relevance of lower PPI as an objective biological correlate of anxiety proneness in pregnant women. These findings call for prospective studies to dissect the multifactorial influences on PPI in relation to mental health of pregnant women.

  5. The Association between COMT, BDNF, and NRG1 and Premorbid Social Functioning in Patients with Psychosis, Their Relatives, and Controls

    Directory of Open Access Journals (Sweden)

    Muriel Walshe

    2012-01-01

    Full Text Available We investigated the influences of putative candidate genes for psychosis on premorbid social adjustment and on premorbid schizoid-schizotypal traits. A family-based sample was used including 177 patients with schizophrenia or bipolar I disorder with a history of psychotic symptoms, 86 of their unaffected relatives, and 116 unrelated healthy controls. Association analyses on the combined sample were conducted using the Statistical Analysis for Genetic Epidemiology software (SAGE and adjusting for age, sex, clinical group, and the family-based nature of the data. The COMT Val158Met and BDNF Val66Met polymorphisms showed no evidence of association with either phenotype. The SNP rs221533 of the NRG1 gene was significantly associated with premorbid adjustment in adolescence with TT homozygous subjects having a poorer performance than C allele carriers. In the context of neurodevelopmental disorders such as schizophrenia and other psychoses, this finding is plausible; however, it is preliminary and requires replication in an independent sample. In a broader sense, the use of intermediate quantitative phenotypes such as the ones presented in this study may be of help to understand the mechanism of action of genetic risk factors.

  6. Impact of aerobic exercise training on cognitive functions and affect associated to the COMT polymorphism in young adults.

    Science.gov (United States)

    Stroth, Sanna; Reinhardt, Ralf K; Thöne, Jan; Hille, Katrin; Schneider, Matthias; Härtel, Sascha; Weidemann, Wolfgang; Bös, Klaus; Spitzer, Manfred

    2010-10-01

    Physical fitness can serve as a means to enhance cognitive functioning by modulating particular aspects of brain functioning. However, mechanisms underlying this modulating effect remain widely unresolved. To examine the impact and to clarify the mechanisms of physical fitness training in a young and healthy population, it was investigated whether an increase in fitness would result in improvements in executive control processes and positive and negative affect. Moreover, genotype of the Val158Met polymorphism in catechol-O-methyltransferase (COMT) as an index of relative central dopamine bioavailability was determined to elucidate dopamine tuning efficiency and its association with performance in the applied cognitive tasks. Seventy-five individuals participated and underwent an incremental fitness test to assess physical fitness. An exercising group subsequently engaged in a 17 weeks running training consisting of three running sessions at moderate to high, individually adjusted intensities. Associated with increased fitness improved cognitive flexibility and cognitive control were observed, whereas working memory remained unaffected. In runners, Val/Val participants improved cognitive performance to a greater extent compared to individuals carrying a Met allele. From the present results it is concluded that an increase in physical fitness provides a means to improve cognitive functioning via dopaminergic modulation.

  7. 解析COMT基因Met多态与子宫内膜异位症的关系%Analysis of the COMT Gene Met Polymorphism with Endometriosis Relationship

    Institute of Scientific and Technical Information of China (English)

    彭莉; 彭娟

    2013-01-01

      目的分析 COMT 基因 Met 多态与子宫内膜异位症的关系。方法选取2011年6月至2012年6月期间于我院就诊的100内膜异位症患者为试验组(其中包括45腺肌病患者),以蛋白酶 K 消化-饱和酚氯仿法对其外周血细胞基因组 DNA 进行提取,并采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法对以上患者进行基因分型,另选取同时期100例未患有子宫内膜异位症(其中包括50例非腺肌病患者)的患者为对照组,采取与试验组同样的方式进行基因分型。结果对比两组 G/G、G/A、A/A 基因型频率,其中试验组分别为38.0%、37.0%、25.0%,对照组分别为40.0%、41.0%、19.0%,两组对比差异性较小,无统计学意,P >0.05;对比两组 A 等位基因频率,试验组为42.3%,对照组为34.1%,两组对比差异性较小,无统计学意义,P >0.05。结论 COMT 基因 Met 多态与子宫内膜异位症无明显相关性。%Objective Analysis of the COMT gene Met polymorphism with endometriosis relationship. Methods From 2011 June to 2012 June in our hospital during the period 100 endometriosis patients into test group (including 45 patients with adenomyosis), with proteinase K digestion - saturated phenol chloroform method on peripheral blood cell genomic DNA extraction, and polymerase chain reaction - restriction fragment length polymorphism ( PCR-RFLP method for more patients ) were genotyped, another takes the same period 100 patients did not suffer from endometriosis ( including 50 cases of patients with adenomyosis ) patients as control group and test group, taking the same way of genotyping. Results Comparison of the two groups of G/G, G/A, A/A genotype frequency, wherein the test group were 38%,37%,25%, the control group were 40%, 41%,19%, two groups of contrast difference is small, no statistical significance,P>0.05;in contrast to the two group of A allele frequencies, experiment group

  8. No Association of BDNF, COMT, MAOA, SLC6A3, and SLC6A4 Genes and Depressive Symptoms in a Sample of Healthy Colombian Subjects

    Directory of Open Access Journals (Sweden)

    Yeimy González-Giraldo

    2015-01-01

    Full Text Available Background. Major depressive disorder (MDD is the second cause of years lived with disability around the world. A large number of studies have been carried out to identify genetic risk factors for MDD and related endophenotypes, mainly in populations of European and Asian descent, with conflicting results. The main aim of the current study was to analyze the possible association of five candidate genes and depressive symptoms in a Colombian sample of healthy subjects. Methods and Materials. The Spanish adaptation of the Hospital Anxiety and Depression Scale (HADS was applied to one hundred eighty-eight healthy Colombian subjects. Five functional polymorphisms were genotyped using PCR-based assays: BDNF-Val66Met (rs6265, COMT-Val158Met (rs4680, SLC6A4-HTTLPR (rs4795541, MAOA-uVNTR, and SLC6A3-VNTR (rs28363170. Result. We did not find significant associations with scores of depressive symptoms, derived from the HADS, for any of the five candidate genes (nominal p values >0.05. In addition, we did not find evidence of significant gene-gene interactions. Conclusion. This work is one of the first studies of candidate genes for depressive symptoms in a Latin American sample. Study of additional genetic and epigenetic variants, taking into account other pathophysiological theories, will help to identify novel candidates for MDD in populations around the world.

  9. Genetic polymorphisms in CYP1A1, CYP1B1 and COMT genes in Greenlandic Inuit and Europeans

    Directory of Open Access Journals (Sweden)

    Mandana Ghisari

    2013-06-01

    Full Text Available Background. The Indigenous Arctic population is of Asian descent, and their genetic background is different from the Caucasian populations. Relatively little is known about the specific genetic polymorphisms in genes involved in the activation and detoxification mechanisms of environmental contaminants in Inuit and its relation to health risk. The Greenlandic Inuit are highly exposed to legacy persistent organic pollutants (POPs such as polychlorinated biphenyls (PCBs and organochlorine pesticides (OCPs, and an elucidation of gene–environment interactions in relation to health risks is needed. Objectives. The aim of this study was to determine and compare the genotype and allele frequencies of the cytochrome P450 CYP1A1 Ile462Val (rs1048943, CYP1B1 Leu432Val (rs1056836 and catechol-O-methyltransferase COMT Val158Met (rs4680 in Greenlandic Inuit (n=254 and Europeans (n=262 and explore the possible relation between the genotypes and serum levels of POPs. Results. The genotype and allele frequency distributions of the three genetic polymorphisms differed significantly between the Inuit and Europeans. For Inuit, the genotype distribution was more similar to those reported for Asian populations. We observed a significant difference in serum polychlorinated biphenyl (CB-153 and the pesticide 1,1-dichloro-2,2-bis(p-chlorophenyl-ethylene (p,p′-DDE levels between Inuit and Europeans, and for Inuit also associations between the POP levels and genotypes for CYP1A1, CYP1B1 and COMT. Conclusion. Our data provide new information on gene polymorphisms in Greenlandic Inuit that might support evaluation of susceptibility to environmental contaminants and warrant further studies.

  10. Brooding rumination and heart rate variability in women at high and low risk for depression: group differences and moderation by COMT genotype.

    Science.gov (United States)

    Woody, Mary L; McGeary, John E; Gibb, Brandon E

    2014-02-01

    There is growing evidence that rumination, perhaps specifically brooding rumination, is a core feature of depression and that it contributes to the development and maintenance of the disorder. A separate line of research has highlighted the role played by heart rate variability (HRV). Both brooding rumination and HRV appear to be driven by disruption in the same neural circuit, heightened amygdala reactivity combined with decreased prefrontal control, and both are highlighted in different units of analysis as reflecting the Research Domain Criteria (RDoC) construct of Loss. However, little is known about the relation among these variables. In the current study, we predicted that higher levels of brooding rumination would be associated with lower levels of HRV and that women at high risk for future depression (i.e., those with a history of past major depressive disorder [MDD]) would exhibit higher levels of brooding and lower levels of HRV. We also examined genetic influences on the variables in this model. We predicted that COMT Val158Met genotype, which has been linked to heightened amygdala reactivity and deficits in prefrontal functioning, would be associated with brooding rumination and HRV, particularly among women with a history of past MDD. The results largely supported our hypotheses, providing additional support for relations among the different units of analysis for the Loss construct.

  11. COMT基因多态性与精神分裂症发病风险及阿立哌唑治疗效应的相关性研究%Association of COMT Gene Polymorphism with Risk of Schizophrenia and Efficacy of Aripiprazole

    Institute of Scientific and Technical Information of China (English)

    李广学; 高树贵; 成佳; 姚文鸣; 郑孝荣; 徐永明

    2014-01-01

    Objective To investigate the association between catechol-O-methyltransferase ( COMT) gene polymorphism and onset risk of schizophrenia , efficacy of aripiprazole.Methods A total of 78 Chinese Han schizophrenic patients and 65 healthy subjects were recruited in this stud-y.All the patients were diagnosed based on the Diagnostic and Statistical Manual of Mental Disorders ( DSM-Ⅳ) .The Positive and Negative Syndrome Scale ( PANSS ) and Clinical Global Impression (CGI) were used to evaluate the clinical efficacy of aripiprazole.Polymerase chain reaction (PCR) and restriction fragment length polymorphism ( RFLP ) were employed to detect COMT geno-types.Results The COMT Val158 Met genotype and allele distributions in schizophrenia patients were significantly different from those in health subjects ( P0.05 ) .Conclusions The polymorphism of COMT gene Val 158/Met is correlated with the onset of schizophrenia , but has no effect on the clinical efficacy of aripiprazole.%目的:探讨儿茶酚氧位甲基转移酶(the catechol-O-methyltransferase, COMT)基因多态性与精神分裂症发病风险及阿立哌唑治疗效应之间的相关性。方法采用病例-对照研究设计,在中国汉族人群中收集78例符合美国精神障碍诊断与统计手册第4版( DSM-Ⅳ)精神分裂症诊断标准的首发精神分裂症患者,并与65例健康志愿者进行对照。用阳性与阴性症状评定量表( PANSS )、临床大体评定量表( CGI )评定阿立哌唑治疗的疗效。运用聚合酶链式反应-限制性片段长度多态分析( PCR-RFLP)方法进行基因分型。结果患者组与正常对照组基因型和等位基因频率分布存在显著性差异( P均<0.05); COMT基因多态性也与精神分裂症患者年龄、病程相关联。经阿立哌唑治疗后,患者精神症状及临床疗效总评分均有明显改善,但其改善程度在3种基因型间比较无明显差异。结论 COMT基因Val158/108 Met

  12. Soy isoflavones, CYP1A1, CYP1B1, and COMT polymorphisms, and breast cancer: a case-control study in southwestern China.

    Science.gov (United States)

    Wang, Qiong; Li, Hui; Tao, Ping; Wang, Yuan-Ping; Yuan, Ping; Yang, Chun-Xia; Li, Jia-Yuan; Yang, Fei; Lee, Hui; Huang, Yuan

    2011-08-01

    CYP1A1, CYP1B1, and COMT are key enzymes involved in estrogen metabolism. Soy isoflavones, phytoestrogens found in soy foods, may modify the activity of these enzymes. A case-control study was conducted to assess the associations between soy isoflavone intake and the CYP1A1 Ile462Val, CYP1B1 Val432Leu, and COMT Val158Met polymorphisms and breast cancer, as well as their combined effects on breast cancer. A total of 400 newly diagnosed breast cancer cases and 400 healthy controls were recruited. Participants' daily intake of soy isoflavones (DISI [mg/day]) was calculated and transformed to energy-adjusted DISI by the residual method. Gene sequencing was used to analyze CYP1A1, CYP1B1, and COMT polymorphisms. Adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) were estimated by conditional logistic regression. A strong protective dose-dependent effect of energy-adjusted DISI on breast cancer was found in both pre- and postmenopausal women (P(trend) CYP1B1 Leu/Leu susceptible genotype carriers had higher risk of breast cancer (aORs > 1, OR 95% CIs exclude 1). In premenopausal women, only carrying CYP1B1 Leu/Leu was associated with breast cancer risk (aOR = 2.05, 95% CI: 1.11-3.79). Carrying CYP1A1 Val/Val was related to breast cancer risk only among all women. A stratified analysis was performed at two levels of energy-adjusted DISI, with wildtype homozygous genotypes and low energy-adjusted DISI as the reference. In the high energy-adjusted DISI subgroup, carrying the CYP1B1 Leu/Leu genotype did not affect breast cancer risk in either all women or in the menopausal subgroups, compared with the reference. Overall, in Han Chinese women, carrying CYP1A1 Val/Val and COMT Met/Met appears to be associated with breast cancer risk, especially in postmenopausal women. CYP1B1 susceptible genotypes (Val/Leu or Leu/Leu) also contribute to increased breast cancer risk, regardless of menopausal status, but high soy isoflavone intake may reduce this risk.

  13. Polimorfismo VAL158MET del gen Catecol-O-Metiltransferasa y características clínicas en primeros episodios de psicosis

    OpenAIRE

    Pelayo Terán, José María

    2011-01-01

    RESUMEN: La esquizofrenia está considerada un síndrome clínico heterogéneo con una etiopatogenia de origen multifactorial, en el que se incluyen factores ambientales, caracteriales y genéticos. A pesar de que más del 50% de la variabilidad de la enfermedad se puede deber a uno o varios factores genéticos, sólo un número limitado de variantes de riesgo genético y con un efecto muy débil han podido ser identificados. Muchos de ellos no han podido reproducirse tanto por la diversidad de las mues...

  14. Antipsychotic-induced tardive dyskinesia and polymorphic variations in COMT, DRD2, CYP1A2 and MnSOD genes: a meta-analysis of pharmacogenetic interactions.

    Science.gov (United States)

    Bakker, P R; van Harten, P N; van Os, J

    2008-05-01

    Despite accumulating evidence pointing to a genetic basis for tardive dyskinesia, results to date have been inconsistent owing to limited statistical power and limitations in molecular genetic methodology. A Medline, EMBASE and PsychINFO search for literature published between 1976 and June 2007 was performed, yielding 20 studies from which data were extracted for calculation of pooled estimates using meta-analytic techniques. Evidence from pooled data for genetic association with tardive dyskinesia (TD) showed (1) in COMT(val158met), using Val-Val homozygotes as reference category, a protective effect for Val-Met heterozygotes (OR=0.63, 95% CI: 0.46-0.86, P=0.004) and Met carriers (OR=0.66, 95% CI: 0.49-0.88, P=0.005); (2) in Taq1A in DRD2, using the A1 variant as reference category, a risk-increasing effect for the A2 variant (OR=1.30, 95% CI: 1.03-1.65, P=0.026), and A2-A2 homozygotes using A1-A1 as reference category (OR=1.80, 95% CI: 1.03-3.15, P=0.037); (3) in MnSOD Ala-9Val, using Ala-Ala homozygotes as reference category, a protective effect for Ala-Val (OR=0.37, 95% CI: 0.17-0.79, P=0.009) and for Val carriers (OR=0.49, 95% CI: 0.24-1.00, P=0.047). These analyses suggest multiple genetic influences on TD, indicative of pharmacogenetic interactions. Although associations are small, the effects underlying them may be subject to interactions with other loci that, when identified, may have acceptable predictive power. Future genetic research will take advantage of new genomic knowledge. Molecular Psychiatry (2008) 13, 544-556; doi:10.1038/sj.mp.4002142; published online 8 January 2008.

  15. Polimorfismo Val108/158Met en el gen dopaminérgico catecol-o-metil transferasa (COMT en una población mixta peruana y su importancia para los estudios neuropsiquiátricos

    Directory of Open Access Journals (Sweden)

    Doris Huerta

    2007-12-01

    Full Text Available Introducción: El gen dopaminérgico catecol-o-metil transferasa (COMT, tiene un polimorfismo funcional Val108/158Met que da lugar a variantes de la enzima que cataliza la o-metilación de las catecolaminas activas, participando en el metabolismo de las drogas y neurotransmisores, como la L-dopa, norepinefrina, epinefrina y dopamina y, por consiguiente, puede asociarse a condiciones neuropsiquiátricas. Objetivos: Determinar las frecuencias genotípicas y alélicas del polimorfismo Val108/158Met del gen COMT en sujetos saludables de una población mixta peruana y establecer las implicancias para el estudio genético de enfermedades y otras condiciones neuropsiquiátricas. Diseño: Estudio descriptivo, observacional, transversal. Lugar: Centro de Investigación de Bioquímica y Nutrición ‘Alberto Guzmán Barrón’. Facultad de Medicina, Universidad Nacional Mayor de San Marcos. Participantes: Ciento seis personas, hombres y mujeres, clínicamente saludables, sin enfermedades neurológicas ni mentales u otra patología similar, voluntarios con consentimiento informado, sin relación de parentesco, todos residentes en Lima, cuyas edades fluctuaban entre los 18 y 50 años. Intervenciones: Extracción del ADN genómico a partir de células de epitelio bucal, según metodología estándar. Amplificación mediante la PCR con primers específicos y digestión con la enzima de restricción NlaIII. Detección de fragmentos de restricción de longitud polimórfica (RFLP por electroforesis en gel de poliacrilamida al 6%, teñido con nitrato de plata. Principales medidas de resultados: Frecuencias genotípicas y alélicas del gen COMT en población mixta peruana. Resultados: Se encontró las frecuencias genotípicas Met/Met=0,0661, Val/Met=0,5094 y Val/Val=0,4245, siendo la distribución consistente con el equilibrio de Hardy-Weinberg (X² =3,0317, g.l.=1, p >0,05. Las frecuencias alélicas encontradas fueron alelo Val=0,68 y el alelo Met=0

  16. Dopamine metabolism in adults with 22q11 deletion syndrome, with and without schizophrenia--relationship with COMT Val¹⁰⁸/¹⁵⁸Met polymorphism, gender and symptomatology

    NARCIS (Netherlands)

    E. Boot; J. Booij; N. Abeling; J. Meijer; F. da Silva Alves; J. Zinkstok; F. Baas; D. Linszen; T. van Amelsvoort

    2011-01-01

    22q11 Deletion syndrome (22q11DS) is a major risk factor for schizophrenia. In addition, both conditions are associated with alterations of the dopaminergic system. The catechol-O-methyltransferase (COMT) gene, located within the deleted region, encodes for the enzyme COMT that is important for degr

  17. COMT genotype, gambling activity, and cognition

    DEFF Research Database (Denmark)

    Grant, Jon E; Leppink, Eric W; Redden, Sarah A

    2015-01-01

    gambling. This study examined adults with varying levels of gambling behavior to determine whether COMT genotype was associated with differences in gambling symptoms and cognitive functioning. 260 non-treatment-seeking adults aged 18-29 years with varying degrees of gambling behavior provided saliva...... significantly different from the Val/Met (13.2%) group (p = 0.001). The Val/Val COMT group was also associated with significantly more gambling disorder diagnostic criteria being met, greater frequency of gambling behavior, and significantly worse cognitive performance on the Cambridge Gamble Task (risk...... adjustment and delay aversion) and the Spatial Working Memory task (total errors). This study adds to the growing literature on the role of COMT in impulsive behaviors by showing that the Val/Val genotype was associated with specific clinical and cognitive elements among young adults who gamble...

  18. The effect of COMT gene on the target precision of the athlete movement

    Directory of Open Access Journals (Sweden)

    E. V. Mikhailova

    2014-01-01

    Full Text Available The aim of the study was to find correlation between COMT gene alleles and the target precision of the athlete movement. 68 Russian competing athletes involved in boxing and volleyball, participated in the study. We found interrelation between COMT Met allele and a tall stature in the volleyball players.

  19. COMT基因rs6267多态性与母亲教养行为对青少年身体攻击和关系攻击的交互作用%Interaction between COMT Gene rs6267 Polymorphism and Maternal Parenting Behavior on Adolescents’ Physical and Relational Aggression

    Institute of Scientific and Technical Information of China (English)

    曹丛; 王美萍; 张文新; 纪林芹; 陈亮; 陈欣银

    2014-01-01

    遗传与环境如何交互作用影响儿童青少年的攻击行为是当前攻击研究中的重要前沿课题之一。近年来,分子遗传学关于人类攻击的研究已拓展到对不同攻击亚类(身体攻击和关系攻击)的遗传基础的探讨。本研究运用问卷法与 DNA 分型技术,对1258名儿童进行为时4年(四年级-七年级)的追踪调查,考察COMT基因rs6267多态性与母亲教养行为对青少年身体攻击和关系攻击的交互作用以及性别在其中的调节作用。结果发现, COMT基因rs6267多态性与母亲教养行为仅交互作用于男青少年的身体攻击,母亲教养行为显著预测 GG 基因型男青少年的身体攻击,但对 T 等位基因男青少年身体攻击的预测作用并不显著。COMT 基因 rs6267多态性与母亲教养行为对青少年关系攻击的交互作用不显著。本研究结果表明,身体攻击和关系攻击具有不同遗传基础和发生机制。%The influencing factors and underlying mechanisms of aggressive behavior are important fundamental issues in research on human aggression. With the advancement of molecular genetics, the research on the mechanisms of aggression has reached molecular level in recent years. Recent studies using candidate gene strategy have demonstrated that the COMT (catechol-O-methyltransferase) gene was significantly associated with human aggression. However, existing research mainly focused on physical aggression, while the genetics mechanism of relational aggression has scarcely been investigated. To our knowledge, only two studies examined the genetic underpinnings of the two specific subtypes of aggression by examining the direct associations between COMT gene Val158Met polymorphism and both physical and relational aggression, but these studies failed to investigate the gene-environment interaction. Recent research has revealed a new functionally single nucleotide polymorphism rs6267 in the COMT gene which also plays

  20. The Genetic Influence on the Cortical Processing of Experimental Pain and the Moderating Effect of Pain Status

    NARCIS (Netherlands)

    Vossen, Helen; Kenis, Gunter; Rutten, Bart; Os, van Jim; Hermens, Hermie; Lousberg, Richel

    2010-01-01

    Background: Research suggests that the COMT Val158Met, BDNF Val66Met and OPRM1 A118G polymorphisms moderate the experience of pain. In order to obtain experimental confirmation and extension of findings, cortical processing of experimentally-induced pain was used. - Method: A sample of 78 individua

  1. The Genetic Influence on the Cortical Processing of Experimental Pain and the Moderating Effect of Pain Status

    NARCIS (Netherlands)

    H. Vossen; G. Kenis; B. Rutten; J. van Os; H. Hermens; R. Lousberg

    2010-01-01

    Background Research suggests that the COMT Val158Met, BDNF Val66Met and OPRM1 A118G polymorphisms moderate the experience of pain. In order to obtain experimental confirmation and extension of findings, cortical processing of experimentally-induced pain was used. Method A sample of 78 individuals wi

  2. Are genetic variants of COMT associated with addiction?

    Science.gov (United States)

    Tammimäki, Anne Emilia; Männistö, Pekka T

    2010-12-01

    The human catechol-O-methyl transferase (COMT) gene contains multiple single-nucleotide polymorphisms, some of which are postulated to have clinical significance. This article reviews human studies that have explored the association between COMT polymorphisms and addiction to drugs, alcohol or tobacco. Most studies concentrate on the Val108/158Met polymorphism. Although there are reports indicating a positive association with COMT polymorphisms and addiction, the majority of the studies failed to detect such a link between them with one exception, smoking. It is unlikely that there would be any single gene that could be designated as 'the addiction gene'. Rather, there seems to be a great number of genes that are associated with addiction, among which COMT seems to have a minor role. Environmental factors and genetic milieu have a great impact on whether the small effects of COMT polymorphisms on risk of addiction can be detected in a given population. Sex differences complicate the gene-environment interplay even further.

  3. Functional polymorphism of genes inactivating biogenic amines and cognitive deficits in paranoid schizophrenia [Funkcjonalny polimorfizm genów enzymów inaktywujących aminy biogenne a deficyty procesów poznawczych w schizofrenii paranoidalnej

    Directory of Open Access Journals (Sweden)

    Tylec, Aneta

    2013-04-01

    Full Text Available Aim. The aim of the work was to assess relationship between gene polymorphism of enzymes influencing dopaminergic-, serotoninergic, and noradrenergic transfer and cognitive functioning of paranoid schizophrenic inpatients (ICD-10. Method. The following methods have been used in the study: The Test of Everyday Attention (TEA and The Visual Object and Space Perception Battery (VOSP , psychiatric scales (SAPS, SANS, BDI and techniques of genetic engineering (PCR reaction, RFLP and VNTR techniques. Subject groups included 100 schizophrenic patients (57 male and 50 healthy controls (20 male. Results. The results revealed positive correlation between polymorphism of Val158MetCOMT and cognitive deficits in schizophrenic patients. No statistically significant relationship was elicited between gene polymorphism of Val158Met COMT and VNTR MAO-A in promoter area and schizophrenia onset. Allelic polymorphism of Val158Met OMT and VNTR MAO-A in promoter area did not differ between the subject groups. The patients with genotype Val/Val of polymorphism Val 158MetCOMT showed major cognitive deficits.

  4. Genetic influences on the acquisition and inhibition of fear.

    Science.gov (United States)

    Wendt, Julia; Neubert, Jörg; Lindner, Katja; Ernst, Florian D; Homuth, Georg; Weike, Almut I; Hamm, Alfons O

    2015-12-01

    As a variant of the Pavlovian fear conditioning paradigm the conditional discrimination design allows for a detailed investigation of fear acquisition and fear inhibition. Measuring fear-potentiated startle responses, we investigated the influence of two genetic polymorphisms (5-HTTLPR and COMT Val(158)Met) on fear acquisition and fear inhibition which are considered to be critical mechanisms for the etiology and maintenance of anxiety disorders. 5-HTTLPR s-allele carriers showed a more stable potentiation of the startle response during fear acquisition. Homozygous COMT Met-allele carriers, which had demonstrated delayed extinction in previous investigations, show deficient fear inhibition in presence of a learned safety signal. Thus, our results provide further evidence that 5-HTTLPR and COMT Val(158)Met genotypes influence the vulnerability for the development of anxiety disorders via different mechanisms.

  5. Association of polymorphisms in genes involved in the dopaminergic pathway with blood pressure and uric acid levels in Chinese females.

    Science.gov (United States)

    Yeh, Ting-Kuang; Yeh, Ting-Chi; Weng, Chi-Feng; Shih, Bing-Fu; Tsao, Hsueh-Jen; Hsiao, Chien-Hua; Chuang, Fu-Tai; Hu, Chung-Yi; Chang, Chun-Yen

    2010-12-01

    Since the high degree of heritability of physiological traits was demonstrated by twin and adoption studies, contemporary researchers in the fields of clinical medicine, behavioral science, and genetics have acknowledged the crucial role of genetic factors in human physiology. The study described herein explores the association between physiological parameters and the dopaminergic system using molecular genetic techniques. A total of 558 Taiwanese female volunteers, ranging from 16 to 17 years, were recruited. Single nucleotide polymorphisms in genes involved in the dopaminergic pathway were selected for analysis. Systolic blood pressure and diastolic blood pressure were associated significantly with the catechol-O-methyltransferase (COMT) Val158Met polymorphism and the dopamine β-hydroxylase (DBH) C1021T polymorphism. Furthermore, plasma uric acid was associated significantly with the COMT Val158Met polymorphism. Our study suggests the possible involvement of genetic polymorphisms in COMT and DBH in the regulation of blood pressure and plasma uric acid.

  6. Divergent backward masking performance in schizophrenia and bipolar disorder: association with COMT.

    Science.gov (United States)

    Goghari, Vina M; Sponheim, Scott R

    2008-03-05

    Schizophrenia has been reliably associated with impairments in backward masking performance, while bipolar disorder has less consistently been tied to such a deficit. To examine the genetic determinants of visual perception abnormalities in schizophrenia and bipolar disorder, this study evaluated the diagnostic specificity of backward masking performance deficits and whether masking deficits were associated with catechol-O-methyl transferase (COMT) genotype. A location-based backward masking task, which equated participants on the perceptual intensity of stimuli, was completed by 41 schizophrenia outpatients, 28 bipolar outpatients, and 43 nonpsychiatric controls. COMT genotype data were available for 39 schizophrenia outpatients, 28 bipolar outpatients, and 20 nonpsychiatric controls. Schizophrenia patients demonstrated impaired backward masking performance compared to controls and bipolar patients. A group by COMT genotype interaction was detected with schizophrenia Met homozygotes performing more poorly than control and bipolar Met homozygotes, and worse than Val homozygote and heterozygote schizophrenia patients. This study provides novel evidence for differential effects of the COMT gene on neural systems underlying visual perception in schizophrenia and bipolar disorder. The COMT Met allele may be associated with deficits in schizophrenia that are unrelated to neural systems supporting sustained attention or working memory.

  7. Epistasis analysis for estrogen metabolic and signaling pathway genes on young ischemic stroke patients.

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    Yi-Chen Hsieh

    Full Text Available BACKGROUND: Endogenous estrogens play an important role in the overall cardiocirculatory system. However, there are no studies exploring the hormone metabolism and signaling pathway genes together on ischemic stroke, including sulfotransferase family 1E (SULT1E1, catechol-O-methyl-transferase (COMT, and estrogen receptor α (ESR1. METHODS: A case-control study was conducted on 305 young ischemic stroke subjects aged COMT Val158Met, ESR1 c.454-397 T/C and c.454-351 A/G genes were genotyped and compared between cases and controls to identify single nucleotide polymorphisms associated with ischemic stroke susceptibility. Gene-gene interaction effects were analyzed using entropy-based multifactor dimensionality reduction (MDR, classification and regression tree (CART, and traditional multiple regression models. RESULTS: COMT Val158Met polymorphism showed a significant association with susceptibility of young ischemic stroke among females. There was a two-way interaction between SULT1E1 -64G/A and COMT Val158Met in both MDR and CART analysis. The logistic regression model also showed there was a significant interaction effect between SULT1E1 -64G/A and COMT Val158Met on ischemic stroke of the young (P for interaction = 0.0171. We further found that lower estradiol level could increase the risk of young ischemic stroke for those who carry either SULT1E1 or COMT risk genotypes, showing a significant interaction effect (P for interaction = 0.0174. CONCLUSIONS: Our findings support that a significant epistasis effect exists among estrogen metabolic and signaling pathway genes and gene-environment interactions on young ischemic stroke subjects.

  8. Analysis on association between COMT gene polymorphism and tardive dyskinesia induced by antipsychotic drugs%抗精神分裂症药物诱发迟发性运动障碍与COMT基因多态性的关联性分析

    Institute of Scientific and Technical Information of China (English)

    刘姗姗; 张逸远; 于跃; 孙颖; 赵刚; 孙世龙; 王宝贵; 刘颖

    2011-01-01

    目的:通过分析中国北方汉族人群中精神分裂症患者COMT基因多态性Val158Met 分布,研究COMT基因多态性与精神分裂症及迟发性运动障碍(TD)发生的关系.方法:采集356例并发TD的精神分裂症患者( TD组)、419例不发生TD的精神分裂症患者(非TD组)及471例正常健康人 (正常对照组)的全血样本,提取基因组DNA,应用TaqMan探针检测COMT基因多态性Val158Met基因型和等位基因的分布.结果:正常对照组与精神分裂症组比较,基因型与等位基因频数分布差异均无统计学意义(χ2=3.08,df=3,P=0.21;χ2=2.067,df=2,P=0.15).TD组与正常对照组比较,基因型与等位基因频数分布差异均无统计学意义(χ2=1.857,df=3,P=0.40;χ2 =1.281,df=2,P=0.26).非TD组与正常对照组比较,基因型与等位基因频数分布差异均无统计学意义(χ2=2.505,df=3,P=0.29;χ2=1.709,df=2,P=0.19).TD组与非TD组比较,基因型与等位基因频数分布差异均无统计学意义(χ2=0.021,df=3,P=0.99;χ2=0.013,df=2,P=0.91).结论:精神分裂症的发生与COMT基因多态性Val158Met无关联性,精神分裂症患者并发TD与COMT基因多态性Val158Met无关联性.

  9. Association of COMT and COMT-DRD2 interaction with creative potential

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    Shun eZhang

    2014-04-01

    Full Text Available Several lines of evidence suggest that genes involved in dopamine (DA transmission may contribute to creativity. Among these genes, the catechol-O-methyltransferase gene (COMT and the dopamine D2 receptor gene (DRD2 are the most promising candidates. Our previous study has revealed evidence for the involvement of DRD2 in creative potential. The present study extended our previous study by systematically exploring the association of COMT with creative potential as well as the interaction between COMT and DRD2. Twelve single nucleotide polymorphisms (SNPs covering COMT were genotyped in 543 healthy Chinese college students whose creative potentials were assessed by divergent thinking tests. Single SNP analysis showed that rs174697 was nominally associated with verbal originality, two SNPs (rs737865 and rs5993883 were nominally associated with figural fluency, and two SNPs (rs737865 and rs4680 were nominally associated with figural originality. Haplotype analysis showed that, the TCT and CCT haplotype (rs737865-rs174675-rs5993882 were nominally associated with figural originality, and the TATGCAG and CGCGGGA haplotype (rs4646312-rs6269-rs4633-rs6267-rs4818-rs4680-rs769224 were nominally associated with figural originality and verbal flexibility, respectively. However, none of these nominal findings survived correction for multiple testing. Gene-gene interaction analysis identified one significant four-way interaction of rs174675 (COMT, rs174697 (COMT, rs1076560 (DRD2 and rs4436578 (DRD2 on verbal fluency, one significant four-way interaction of rs174675 (COMT, rs4818 (COMT, rs1076560 (DRD2 and rs4648317 (DRD2 on verbal flexibility, and one significant three-way interaction of rs5993883 (COMT, rs4648319 (DRD2 and rs4648317 (DRD2 on figural flexibility. In conclusion, the present study provides nominal evidence for the involvement of COMT in creative potential and suggests that DA related genes may act in coordination to contribute to creativity.

  10. Epistatic and functional interactions of catechol-o-methyltransferase (COMT and AKT1 on neuregulin1-ErbB signaling in cell models.

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    Yoshitatsu Sei

    Full Text Available BACKGROUND: Neuregulin1 (NRG1-ErbB signaling has been implicated in the pathogenesis of cancer and schizophrenia. We have previously reported that NRG1-stimulated migration of B lymphoblasts is PI3K-AKT1dependent and impaired in patients with schizophrenia and significantly linked to the catechol-o-methyltransferase (COMT Val108/158Met functional polymorphism. METHODOLOGY/PRINCIPAL FINDINGS: We have now examined AKT1 activation in NRG1-stimulated B lymphoblasts and other cell models and explored a functional relationship between COMT and AKT1. NRG1-induced AKT1 phosphorylation was significantly diminished in Val carriers compared to Met carriers in both normal subjects and in patients. Further, there was a significant epistatic interaction between a putatively functional coding SNP in AKT1 (rs1130233 and COMT Val108/158Met genotype on AKT1 phosphorylation. NRG1 induced translocation of AKT1 to the plasma membrane also was impaired in Val carriers, while PIP(3 levels were not decreased. Interestingly, the level of COMT enzyme activity was inversely correlated with the cells' ability to synthesize phosphatidylserine (PS, a factor that attracts the pleckstrin homology domain (PHD of AKT1 to the cell membrane. Transfection of SH-SY5Y cells with a COMT Val construct increased COMT activity and significantly decreased PS levels as well as NRG1-induced AKT1 phosphorylation and migration. Administration of S-adenosylmethionine (SAM rescued all of these deficits. These data suggest that AKT1 function is influenced by COMT enzyme activity through competition with PS synthesis for SAM, which in turn dictates AKT1-dependent cellular responses to NRG1-mediated signaling. CONCLUSION/SIGNIFICANCE: Our findings implicate genetic and functional interactions between COMT and AKT1 and may provide novel insights into pathogenesis of schizophrenia and other ErbB-associated human diseases such as cancer.

  11. Association of Single Nucleotide Polymorphisms in CYP1B1 and COMT Genes with Breast Cancer Susceptibility in Indian Women

    OpenAIRE

    Sharawan Yadav; Naveen Kumar Singhal; Virendra Singh; Neeraj Rastogi; Pramod Kumar Srivastava; Mahendra Pratap Singh

    2009-01-01

    Cytochrome P450 1B1 (CYP1B1) and catechol-$O$-methyltransferase (COMT) enzymes play critical roles in estrogen metabolism. Alterations in the catalytic activity of CYP1B1 and COMT enzymes have been found associated with altered breast cancer risk in postmenopausal women in many populations. The substitution of leucine (Leu) to valine (Val) at codon 432 increases the catalytic activity of CYP1B1, however, substitution of Val to methionine (Met) at codon 158 decreases the catalytic activity of ...

  12. Association of catechol-O-methyltransferase Val(108/158) Met genetic polymorphism with schizophrenia, P50 sensory gating, and negative symptoms in a Chinese population.

    Science.gov (United States)

    Mao, Qiao; Tan, Yun-Long; Luo, Xing-Guang; Tian, Li; Wang, Zhi-Ren; Tan, Shu-Ping; Chen, Song; Yang, Gui-Gang; An, Hui-Mei; Yang, Fu-De; Zhang, Xiang-Yang

    2016-08-30

    Catechol-O-methyltransferase (COMT), an enzyme involved in the degradation and inactivation of the neurotransmitter dopamine, is associated with the sensory gating phenomenon, protecting the cerebral cortex from information overload. The COMT Val(108/158)Met polymorphism is essential for prefrontal cortex processing capacity and efficiency. The current study was designed to investigate the role of COMT Val(108/158)Met polymorphism in development, sensory gating deficit, and symptoms of schizophrenia in Han Chinese population. P50 gating was determined in 139 schizophrenic patients and 165 healthy controls. Positive and Negative Syndrome Scale (PANSS) was used to assess the clinical symptomatology in 370 schizophrenic subjects. COMT Val(108/158)Met polymorphism was genotyped by PCR-restriction fragment length polymorphism (PCR-RFLP). No significant differences in COMT allele and genotype distributions were observed between schizophrenic patients and control groups. Although P50 deficits were present in patients, there was no evidence for an association between COMT Val(108/158)Met polymorphism and the P50 biomarker. Moreover, PANSS negative subscore was significantly higher in Val allele carriers than in Met/Met individuals. The present findings suggest that COMT Val(108/158)Met polymorphism may not contribute to the risk of schizophrenia and to the P50 deficits, but may contribute to the negative symptoms of schizophrenia among Han Chinese.

  13. Association of Single Nucleotide Polymorphisms in Catechol-O-Methyltransferase and Serine-Threonine Protein Kinase Genes in the Pakistani Schizophrenic Population: A Study with Special Emphasis on Cannabis and Smokeless Tobacco.

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    Nawaz, Rukhsana; Siddiqui, Sonia

    2015-01-01

    Schizophrenia is a neuropsychiatric disorder in which abnormalities in the prefrontal cortex lead to impaired synthesis of dopamine. It is associated with hallucination, psychosis and hearing impairments. Many susceptible genes have been identified in schizophrenia such as catechol-O-methyltransferase (COMT) and serine/threonine kinase (AKT1). Single nucleotide polymorphisms (SNPs) in these genes have not been identified in Pakistan. Therefore, we investigated the allelic and genotypic frequencies in COMT and AKT1 genes in the Pakistani population. Polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP) and DNA sequencing were used to identify SNPs in the genes. The present study shows that COMT Val and COMT Met allelic frequencies for the controls were p=0.52, q=0.48 and for the schizophrenic cases they were p=0.34, q=0.66 respectively. The distribution of polymorphism in COMT Val158Met genotype by Hardy-Weinberg equilibrium (HWE) was P=0.61 for controls and P=0.005 for cases. The data reveal that SNP rs1130214 T allele mutation was found neither in patients nor in controls in the 5' untranslated region (UTR). This proves that no association of AKT1 and positive association of COMT with schizophrenia exist in the population of Pakistan. Moreover, a study based on a single family showed COMT Met allele inheritance in schizophrenic offspring. This suggested that COMT allele alteration influences susceptibility to at least some forms of psychosis in the Pakistani population. Interestingly, according to our socio-economical survey, COMT genotype has no association with cannabis but it is strongly associated with tobacco. The Pakistani population with Val158Met SNP showed more susceptibility towards developing schizophrenia. This study highlights the genetic differences between Pakistani and other Caucasian populations.

  14. Augusto Comte e o "positivismo" redescobertos

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    Gustavo Biscaia de Lacerda

    2009-10-01

    Full Text Available Neste ensaio abordamos algumas pesquisas que, nos últimos dez anos ou mais, têm recuperado a obra do fundador do Positivismo, Augusto Comte. Essa recuperação consiste em perceber os trabalhos de Comte em sua inteireza e a partir de sua lógica interna, enfatizando em particular a sua segunda grande obra, o Système de politique positive (1851-1854, e as suas contribuições para a reflexão social e política contemporânea. A fim de tornar inteligível a novidade dessas novas pesquisas, apresentamos uma das narrativas-padrão a respeito de Comte e do Positivismo - no caso, a partir dos escritos de Anthony Giddens -; além disso, fazemos uma discussão sobre o significado da palavra "Positivismo" e as várias correntes teóricas subsumidas em tal expressão.

  15. The lack of association between catechol-O-methyl-transferase Val108/158Met polymorphism and smoking in schizophrenia and alcohol dependence

    OpenAIRE

    Nikolac, Matea; Šagud, Marina; Nedić, Gordana; Nenadić Šviglin, Korona; Mihaljević Peleš, Alma; Uzun, Suzana; Vuskan Čusa, Bjanka; Kozumplik, Oliver; Živković, Maja; Mustapić, Maja; Jakovljević, Miro; PAVLOVIĆ, Mladen; Muck-Šeler, Dorotea; Borovečki, Fran; Pivac, Nela

    2013-01-01

    The study elucidated the association between the COMT Val108/158Met polymorphism and smoking in patients with schizophrenia, patients with alcohol dependence and healthy control subjects. The stepwise logistic regression (odds ratio (OR)=1.56, 95% confidence interval (CI)=1.10–2.23, P=0.014) and the χ2 test (P=0.008) revealed that the COMT Val/Val genotype was significantly associated with smoking in healthy male subjects. Although the hypothesis of the study was that COMT Val108/158Met genot...

  16. Brain white matter structure and COMT gene are linked to second-language learning in adults.

    Science.gov (United States)

    Mamiya, Ping C; Richards, Todd L; Coe, Bradley P; Eichler, Evan E; Kuhl, Patricia K

    2016-06-28

    Adult human brains retain the capacity to undergo tissue reorganization during second-language learning. Brain-imaging studies show a relationship between neuroanatomical properties and learning for adults exposed to a second language. However, the role of genetic factors in this relationship has not been investigated. The goal of the current study was twofold: (i) to characterize the relationship between brain white matter fiber-tract properties and second-language immersion using diffusion tensor imaging, and (ii) to determine whether polymorphisms in the catechol-O-methyltransferase (COMT) gene affect the relationship. We recruited incoming Chinese students enrolled in the University of Washington and scanned their brains one time. We measured the diffusion properties of the white matter fiber tracts and correlated them with the number of days each student had been in the immersion program at the time of the brain scan. We found that higher numbers of days in the English immersion program correlated with higher fractional anisotropy and lower radial diffusivity in the right superior longitudinal fasciculus. We show that fractional anisotropy declined once the subjects finished the immersion program. The relationship between brain white matter fiber-tract properties and immersion varied in subjects with different COMT genotypes. Subjects with the Methionine (Met)/Valine (Val) and Val/Val genotypes showed higher fractional anisotropy and lower radial diffusivity during immersion, which reversed immediately after immersion ended, whereas those with the Met/Met genotype did not show these relationships. Statistical modeling revealed that subjects' grades in the language immersion program were best predicted by fractional anisotropy and COMT genotype.

  17. [The dentistry of Blainville and the positivism of Comte].

    Science.gov (United States)

    Gysel, C

    1989-01-01

    COMTE improved BLAINVILLE's acquaintance when he was the secretary of SAINT-SIMON. They became friends. BLAINVILLE aided COMTE in his illness and financial troubles, taught him biology and was one of the first to support his philosophical ideas, through which he became self-conscious of his own value and scientific methods.

  18. Chromatographic design for the purification of recombinant human membrane COMT

    OpenAIRE

    Santos, Fátima Raquel Milhano dos

    2012-01-01

    Several studies suggest that membrane form of catechol-O-methyltransferase OMT (MB-COMT) is the main responsible for O-methylation at physiologically low concentrations of catecholamines. Despite this, until now no studies have been allowed the total isolation of MB-COMT. Then, a sustainable chromatographic step should be developed in order to obtain significant quantities of active and pure enzyme for posterior application on biochemical, kinetic and structural studies. For the first time, w...

  19. Subtle gene-environment interactions driving paranoia in daily life.

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    Simons, C J P; Wichers, M; Derom, C; Thiery, E; Myin-Germeys, I; Krabbendam, L; van Os, J

    2009-02-01

    It has been suggested that genes impact on the degree to which minor daily stressors cause variation in the intensity of subtle paranoid experiences. The objective of the present study was to test the hypothesis that catechol-O-methyltransferase (COMT) Val(158)Met and brain-derived neurotrophic factor (BDNF) Val(66)Met in part mediate genetic effects on paranoid reactivity to minor stressors. In a general population sample of 579 young adult female twins, on the one hand, appraisals of (1) event-related stress and (2) social stress and, on the other hand, feelings of paranoia in the flow of daily life were assessed using momentary assessment technology for five consecutive days. Multilevel regression analyses were used to examine moderation of daily life stress-induced paranoia by COMT Val(158)Met and BDNF Val(66)Met genotypes. Catechol-O-methyltransferase Val carriers displayed more feelings of paranoia in response to event stress compared with Met carriers. Brain-derived neurotrophic factor Met carriers showed more social-stress-induced paranoia than individuals with the Val/Val genotype. Thus, paranoia in the flow of daily life may be the result of gene-environment interactions that can be traced to different types of stress being moderated by different types of genetic variation.

  20. No association between catechol-o-methyltransferase Val108/158Met polymorphism and schizophrenia or its clinical symptomatology in a Mexican population.

    Science.gov (United States)

    Tovilla-Zárate, Carlos; Medellín, Beatriz Camarena; Fresán, Ana; López-Narváez, Lilia; Castro, Thelma Beatriz Gonzalez; Juárez Rojop, Isela; Ramírez-Bello, Julián; Genis, Alma; Nicolini, Humberto

    2013-02-01

    The gene coding for catecol-o-methyltransferase (COMT), participant in the metabolism of catecholamines, has long been implicated as a candidate gene for schizophrenia. We determined the relation of the COMT Val108/158Met polymorphism with schizophrenia or its symptomatology (negative, disorganized and psychotic dimension). We conducted a case-control study comprising 186 patients with schizophrenia and 247 controls. The diagnosis of schizophrenia was established using the DSM-IV criteria for this illness. The clinical symptomatology was assessed through the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms. No significant differences were found in the distribution of alleles (χ2 = 0.01, df = 1, p = 0.90) or genotypes (χ2 = 1.66, df = 2, p = 0.43) between schizophrenic patients and the control group. Multivariate analysis showed that the COMT Val108/158Met polymorphism has no influence in the clinical symptomatology of schizophrenia. Our results showed no association between COMT Val108/158Met and schizophrenia or evidence for an association between COMT and the clinical symptomatology of this illness. This suggests that the COMT gene may not contribute to the risk for schizophrenia among the Mexican population.

  1. The role of catechol-O-methyl transferase Val(108/158Met polymorphism (rs4680 in the effect of green tea on resting energy expenditure and fat oxidation: a pilot study.

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    Rick Hursel

    Full Text Available INTRODUCTION: Green tea(GT is able to increase energy expenditure(EE and fat oxidation(FATox via inhibition of catechol-O-methyl transferase(COMT by catechins. However, this does not always appear unanimously because of large inter-individual variability. This may be explained by different alleles of the functional COMT Val108/158Met polymorphism that are associated with COMT enzyme activity; high-activity enzyme, COMT(H(Val/Val genotype, and low-activity COMT(L(Met/Met genotype. METHODS: Fourteen Caucasian subjects (BMI: 22.2±2.3 kg/m2, age: 21.4±2.2 years of whom 7 with the COMT(H-genotype and 7 with the COMT(L-genotype were included in a randomized, cross-over study in which EE and substrate oxidation were measured with a ventilated-hood system after decaffeinated GT and placebo(PL consumption. RESULTS: At baseline, EE, RQ, FATox and carbohydrate oxidation(CHOox did not differ between groups. Significant interactions were observed between COMT genotypes and treatment for RQ, FATox and CHOox (p<0.05. After GT vs. PL, EE(GT: 62.2 vs. PL: 35.4 kJ.3.5 hrs; p<0.01, RQ(GT: 0.80 vs. PL: 0.83; p<0.01, FATox(GT: 18.3 vs. PL: 15.3 g/d; p<0.001 and CHOox(GT: 18.5 vs. PL: 24.3 g/d; p<0.001 were significantly different for subjects carrying the COMT(H genotype, but not for subjects carrying the COMT(L genotype (EE, GT: 60.3 vs. PL: 51.7 kJ.3.5 hrs; NS, (RQ, GT: 0.81 vs. PL: 0.81; NS, (FATox, GT: 17.3 vs. PL: 17.0 g/d; NS, (CHOox, GT: 22.1 vs. PL: 21.4 g/d; NS. CONCLUSION: Subjects carrying the COMT(H genotype increased energy expenditure and fat-oxidation upon ingestion of green tea catechins vs, placebo, whereas COMT(L genotype carriers reacted similarly to GT and PL ingestion. The differences in responses were due to the different responses on PL ingestion, but similar responses to GT ingestion, pointing to different mechanisms. The different alleles of the functional COMT Val108/158Met polymorphism appear to play a role in the inter

  2. Race Moderates the Association of Catechol-O-methyltransferase Genotype and Posttraumatic Stress Disorder in Preschool Children

    Science.gov (United States)

    Humphreys, Kathryn L.; Scheeringa, Michael S.

    2014-01-01

    Abstract Objective: The present study sought to replicate previous findings of an association between the Catechol-O-methyltransferase (COMT) val158met polymorphism with posttraumatic stress disorder (PTSD) and symptomatology in a novel age group, preschool children. Methods: COMT genotype was determined in a sample of 171 3–6-year-old trauma-exposed children. PTSD was assessed with a semistructured interview. Accounting for sex, trauma type, and age, genotype was examined in relation to categorical and continuous measures of PTSD both controlling for race and within the two largest racial categories (African American [AA] and European American [EA]). Results: Race significantly moderated the association between genotype and PTSD. Specifically, the genotype associated with increased PTSD symptoms in one racial group had the opposite association in the other racial group. For AA children the met/met genotype was associated with more PTSD symptoms. However, for EA children, val allele carriers had more PTSD symptoms. Whereas every AA child with the met/met genotype met criteria for PTSD, none of the EA children with the met/met genotype did. This genetic association with COMT genotype, in both races but in opposite directions, was most associated with increased arousal symptoms. Conclusions: These findings replicate previous findings in participants of African descent, highlight the moderating effect of race on the association between COMT genotype and PTSD, and provide direct evidence that consideration of population stratification within gene-by-environment studies is valuable to prevent false negative findings. PMID:25329975

  3. Association between catechol-O-methyltrasferase Val108/158Met genotype and prefrontal hemodynamic response in schizophrenia.

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    Ryu Takizawa

    Full Text Available BACKGROUND: "Imaging genetics" studies have shown that brain function by neuroimaging is a sensitive intermediate phenotype that bridges the gap between genes and psychiatric conditions. Although the evidence of association between functional val108/158met polymorphism of the catechol-O-methyltransferase gene (COMT and increasing risk for developing schizophrenia from genetic association studies remains to be elucidated, one of the most topical findings from imaging genetics studies is the association between COMT genotype and prefrontal function in schizophrenia. The next important step in the translational approach is to establish a useful neuroimaging tool in clinical settings that is sensitive to COMT variation, so that the clinician could use the index to predict clinical response such as improvement in cognitive dysfunction by medication. Here, we investigated spatiotemporal characteristics of the association between prefrontal hemodynamic activation and the COMT genotype using a noninvasive neuroimaging technique, near-infrared spectroscopy (NIRS. METHODOLOGY/PRINCIPAL FINDINGS: Study participants included 45 patients with schizophrenia and 60 healthy controls matched for age and gender. Signals that are assumed to reflect regional cerebral blood volume were monitored over prefrontal regions from 52-channel NIRS and compared between two COMT genotype subgroups (Met carriers and Val/Val individuals matched for age, gender, premorbid IQ, and task performance. The [oxy-Hb] increase in the Met carriers during the verbal fluency task was significantly greater than that in the Val/Val individuals in the frontopolar prefrontal cortex of patients with schizophrenia, although neither medication nor clinical symptoms differed significantly between the two subgroups. These differences were not found to be significant in healthy controls. CONCLUSIONS/SIGNIFICANCE: These data suggest that the prefrontal NIRS signals can noninvasively detect the impact

  4. Dopamine system genes are associated with orienting bias among healthy individuals.

    Science.gov (United States)

    Zozulinsky, Polina; Greenbaum, Lior; Brande-Eilat, Noa; Braun, Yair; Shalev, Idan; Tomer, Rachel

    2014-09-01

    Healthy individuals display subtle orienting bias, manifested as a tendency to direct greater attention toward one hemispace, and evidence suggests that this bias reflects an individual trait, which may be modulated by asymmetric dopamine signaling in striatal and frontal regions. The current study examined the hypothesis that functional genetic variants within dopaminergic genes (DAT1 3' VNTR, dopamine D2 receptor Taq1A (rs1800497) and COMT Val158Met (rs4680)) contribute to individual differences in orienting bias, as measured by the greyscales paradigm, in a sample of 197 young healthy Israeli Jewish participants. For the Taq1A variant, homozygous carriers of the A2 allele displayed significantly increased leftward orienting bias compared to the carriers of the A1 allele. Additionally, and as previously reported by others, we found that bias towards leftward orienting of attention was significantly greater among carriers of the 9-repeat allele of the DAT1 3' VNTR as compared to the individuals who were homozygous for the 10-repeat allele. No significant effect of the COMT Val158Met on orienting bias was found. Taken together, our findings support the potential influence of genetic variants on inter-individual differences in orienting bias, a phenotype relevant to both normal and impaired cognitive processes.

  5. The catechol-O-methyltransferase gene (COMT) and cognitive function from childhood through adolescence.

    Science.gov (United States)

    Gaysina, Darya; Xu, Man K; Barnett, Jennifer H; Croudace, Tim J; Wong, Andrew; Richards, Marcus; Jones, Peter B

    2013-02-01

    Genetic variation in the catechol-O-methyltransferase gene (COMT) can influence cognitive function, and this effect may depend on developmental stage. Using a large representative British birth cohort, we investigated the effect of COMT on cognitive function (verbal and non-verbal) at ages 8 and 15 years taking into account the possible modifying effect of pubertal stage. Five functional COMT polymorphisms, rs6269, rs4818, rs4680, rs737865 and rs165599 were analysed. Associations between COMT polymorphisms and cognition were tested using regression and latent variable structural equation modelling (SEM). Before correction for multiple testing, COMT rs737865 showed association with reading comprehension, verbal ability and global cognition at age 15 years in pubescent boys only. Although there was some evidence for age- and sex-specific effects of the COMT rs737865 none remained significant after correction for multiple testing. Further studies are necessary in order to make firmer conclusions.

  6. Dopaminergic and Serotonergic Genotypes and the Subjective Experiences of Hypnosis.

    Science.gov (United States)

    Katonai, E R; Szekely, Anna; Vereczkei, A; Sasvari-Szekely, Maria; Bányai, Éva I; Varga, Katalin

    2017-01-01

    Hypnotizability is related to the Val(158)Met polymorphism of the COMT gene. The authors' aim was to find associations between candidate genes and subjective dimensions of hypnosis; 136 subjects participated in hypnosis and noninvasive DNA sampling. The phenomenological dimensions were tapped by the Archaic Involvement Measure (AIM), the Phenomenology of Consciousness Inventory (PCI), and the Dyadic Interactional Harmony Questionnaire (DIH). The main results were that the "Need of dependence" subscale of AIM was associated with the COMT genotypes. The GG subgroup showed higher scores, whereas AA had below average scores on the majority of the subjective measures. An association between the 5-HTTLPR polymorphism and the intimacy scores on the DIH was also evident. The effects are discussed in the social-psychobiological model of hypnosis.

  7. Family-based association study of the BDNF, COMT and serotonin transporter genes and DSM-IV bipolar-I disorder in children

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    Biederman Joseph

    2009-02-01

    Full Text Available Abstract Background Over the past decade pediatric bipolar disorder has gained recognition as a potentially more severe and heritable form of the disorder. In this report we test for association with genes coding brain-derived neurotrophic factor (BDNF, the serotonin transporter (SLC6A4, and catechol-O-methyltransferase (COMT. Methods Bipolar-I affected offspring triads (N = 173 were drawn from 522 individuals with 2 parents in 332 nuclear families recruited for genetic studies of pediatric psychopathology at the Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD at Massachusetts General Hospital. Results We failed to identify an association with the val66 allele in BDNF (OR = 1.23, p = 0.36, the COMT-l allele (OR = 1.27, p = 0.1, or the HTTLPR short allele (OR = 0.87, p = 0.38. Conclusion Our study suggests that the markers examined thus far in COMT and SLC6A4 are not associated with pediatric bipolar disorder and that if the val66met marker in BDNF is associated with pediatric bipolar disorder the magnitude of the association is much smaller than first reported.

  8. Acute effects of cocaine and cannabis on reversal learning as a function of COMT and DRD2 genotype.

    Science.gov (United States)

    Spronk, Desirée B; Van der Schaaf, Marieke E; Cools, Roshan; De Bruijn, Ellen R A; Franke, Barbara; van Wel, Janelle H P; Ramaekers, Johannes G; Verkes, Robbert J

    2016-01-01

    Long-term cannabis and cocaine use has been associated with impairments in reversal learning. However, how acute cannabis and cocaine administration affect reversal learning in humans is not known. In this study, we aimed to establish the acute effects of administration of cannabis and cocaine on valence-dependent reversal learning as a function of DRD2 Taq1A (rs1800497) and COMT Val108/158Met (rs4680) genotype. A double-blind placebo-controlled randomized 3-way crossover design was used. Sixty-one regular poly-drug users completed a deterministic reversal learning task under the influence of cocaine, cannabis, and placebo that enabled assessment of both reward- and punishment-based reversal learning. Proportion correct on the reversal learning task was increased by cocaine, but decreased by cannabis. Effects of cocaine depended on the DRD2 genotype, as increases in proportion correct were seen only in the A1 carriers, and not in the A2/A2 homozygotes. COMT genotype did not modulate drug-induced effects on reversal learning. These data indicate that acute administration of cannabis and cocaine has opposite effects on reversal learning. The effects of cocaine, but not cannabis, depend on interindividual genetic differences in the dopamine D2 receptor gene.

  9. Association between Val108/158Met polymorphism of catechol-O-methyl transferase gene and anxiety%儿茶酚氧位甲基转移酶基因多态性与焦虑症的相关性研究

    Institute of Scientific and Technical Information of China (English)

    高力舒; 谢健

    2011-01-01

    Objective To explore the relationship of the Val108/158Met polymorphism of Catechol-O-methyl transferase(COMT)gene and anxiety in Han population.Methods The COMT Val108/158Metpolymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism(PCRRFLP)among 176 patients and 200 health subjects.The clinical symptom phenotypes data were obtained by assessing the HAMA and SCL-90 in anxiety patients.Results The distribution frequencies of Met/Met genotype and Met allele were 6.25%.2.50%and 26.99%.18.75%in patients and controls,respectively.Both distribution frequencies were significantly different in two groups,especially in females (P0.05).Following analyzing the clinical symptom phenotypes,the patients with COMT 108/158Met/Met genotype or Met allelic locus had higher HAMA,SCL-90 anxiety and phobic scores than those with other genotypes or Val allelic locus (P0.05).(2)患者组内COMT 108/158Met/Met基因型和携带Met等位基因患者HAMA总分、焦虑和恐怖因子分值分别高于其他基因型和携带Val等位基因患者(P均<0.05).结论 携带COMT Met108/158女性可能更易患焦虑症,COMT Met108/158与临床焦虑和恐怖程度有关.

  10. Catechol-O-Methyltransferase "Val[superscript 158]Met" Genotype, Parenting Practices and Adolescent Alcohol Use: Testing the Differential Susceptibility Hypothesis

    Science.gov (United States)

    Laucht, Manfred; Blomeyer, Dorothea; Buchmann, Arlette F.; Treutlein, Jens; Schmidt, Martin H.; Esser, Gunter; Jennen-Steinmetz, Christine; Rietschel, Marcella; Zimmermann, Ulrich S.; Banaschewski, Tobias

    2012-01-01

    Background: Recently, first evidence has been reported for a gene-parenting interaction (G x E) with regard to adolescent alcohol use. The present investigation set out to extend this research using the catechol-O-methyltransferase ("COMT") "Val[superscript 158]Met" polymorphism as a genetic susceptibility factor. Moreover, the current study…

  11. Pain modality- and sex-specific effects of COMT genetic functional variants.

    Science.gov (United States)

    Belfer, Inna; Segall, Samantha K; Lariviere, William R; Smith, Shad B; Dai, Feng; Slade, Gary D; Rashid, Naim U; Mogil, Jeffrey S; Campbell, Claudia M; Edwards, Robert R; Liu, Qian; Bair, Eric; Maixner, William; Diatchenko, Luda

    2013-08-01

    The enzyme catechol-O-methyltransferase (COMT) metabolizes catecholamine neurotransmitters involved in a number of physiological functions, including pain perception. Both human and mouse COMT genes possess functional polymorphisms contributing to interindividual variability in pain phenotypes such as sensitivity to noxious stimuli, severity of clinical pain, and response to pain treatment. In this study, we found that the effects of Comt functional variation in mice are modality specific. Spontaneous inflammatory nociception and thermal nociception behaviors were correlated the most with the presence of the B2 SINE transposon insertion residing in the 3'UTR mRNA region. Similarly, in humans, COMT functional haplotypes were associated with thermal pain perception and with capsaicin-induced pain. Furthermore, COMT genetic variations contributed to pain behaviors in mice and pain ratings in humans in a sex-specific manner. The ancestral Comt variant, without a B2 SINE insertion, was more strongly associated with sensitivity to capsaicin in female vs male mice. In humans, the haplotype coding for low COMT activity increased capsaicin-induced pain perception in women, but not men. These findings reemphasize the fundamental contribution of COMT to pain processes, and provide a fine-grained resolution of this contribution at the genetic level that can be used to guide future studies in the area of pain genetics.

  12. Brain catechol-O-methyltransferase (COMT) inhibition by tolcapone counteracts recognition memory deficits in normal and chronic phencyclidine-treated rats and in COMT-Val transgenic mice.

    Science.gov (United States)

    Detrait, Eric R; Carr, Greg V; Weinberger, Daniel R; Lamberty, Yves

    2016-08-01

    The critical involvement of dopamine in cognitive processes has been well established, suggesting that therapies targeting dopamine metabolism may alleviate cognitive dysfunction. Catechol-O-methyl transferase (COMT) is a catecholamine-degrading enzyme, the substrates of which include dopamine, epinephrine, and norepinephrine. The present work illustrates the potential therapeutic efficacy of COMT inhibition in alleviating cognitive impairment. A brain-penetrant COMT inhibitor, tolcapone, was tested in normal and phencyclidine-treated rats and COMT-Val transgenic mice. In a novel object recognition procedure, tolcapone counteracted a 24-h-dependent forgetting of a familiar object as well as phencyclidine-induced recognition deficits in the rats at doses ranging from 7.5 to 30 mg/kg. In contrast, entacapone, a COMT inhibitor that does not readily cross the blood-brain barrier, failed to show efficacy at doses up to 30 mg/kg. Tolcapone at a dose of 30 mg/kg also improved novel object recognition performance in transgenic mice, which showed clear recognition deficits. Complementing earlier studies, our results indicate that central inhibition of COMT positively impacts recognition memory processes and might constitute an appealing treatment for cognitive dysfunction related to neuropsychiatric disorders.

  13. Executive functions and selective attention are favored in middle-aged healthy women carriers of the Val/Val genotype of the catechol-o-methyltransferase gene: a behavioral genetic study

    Directory of Open Access Journals (Sweden)

    Gutiérrez-Muñoz Mayra

    2010-10-01

    Full Text Available Abstract Background Cognitive deficits such as poor memory, the inability to concentrate, deficits in abstract reasoning, attention and set-shifting flexibility have been reported in middle-aged women. It has been suggested that cognitive decline may be due to several factors which include hormonal changes, individual differences, normal processes of aging and age-related changes in dopaminergic neurotransmission. Catechol-O-methyltransferase (COMT, a common functional polymorphism, has been related to executive performance in young healthy volunteers, old subjects and schizophrenia patients. The effect of this polymorphism on cognitive function in middle-aged healthy women is not well known. The aim of the current study was to investigate whether measures of executive function, sustained attention, selective attention and verbal fluency would be different depending on the COMT genotype and task demand. Method We genotyped 74 middle-aged healthy women (48 to 65 years old for the COMT Val158Met polymorphism. We analyzed the effects of this polymorphism on executive functions (Wisconsin Card Sorting Test, selective attention (Stroop test, sustained attention (Continuous Performance Test and word generation (Verbal Fluency test, which are cognitive functions that involve the frontal lobe. Results There were 27 women with the Val/Val COMT genotype, 15 with the Met/Met genotype, and 32 with the Val/Met genotype. Women carriers of the Val/Val genotype performed better in executive functions, as indicated by a lower number of errors committed in comparison with the Met/Met or Val/Met groups. The correct responses on selective attention were higher in the Val/Val group, and the number of errors committed was higher in the Met/Met group during the incongruence trial in comparison with the Val/Val group. Performance on sustained attention and the number of words generated did not show significant differences between the three genotypes. Conclusion These

  14. Met in Urological Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Miyata, Yasuyoshi, E-mail: int.doc.miya@m3.dion.ne.jp; Asai, Akihiro; Mitsunari, Kensuke; Matsuo, Tomohiro; Ohba, Kojiro; Mochizuki, Yasushi; Sakai, Hideki [Department of Urology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501 (Japan)

    2014-12-16

    Met is a tyrosine kinase receptor that is considered to be a proto-oncogene. The hepatocyte growth factor (HGF)-Met signaling system plays an important role in tumor growth, invasion, and metastasis in many types of malignancies. Furthermore, Met expression has been reported to be a useful predictive biomarker for disease progression and patient survival in these malignancies. Many studies have focused on the clinical significance and prognostic role of Met in urological cancers, including prostate cancer (PCa), renal cell carcinoma (RCC), and urothelial cancer. Several preclinical studies and clinical trials are in progress. In this review, the current understanding of the pathological role of Met in cancer cell lines, its clinical significance in cancer tissues, and its predictive value in patients with urological cancers are summarized. In particular, Met-related malignant behavior in castration-resistant PCa and the different pathological roles Met plays in papillary RCC and other histological types of RCC are the subjects of focus. In addition, the pathological significance of phosphorylated Met in these cancers is shown. In recent years, Met has been recognized as a potential therapeutic target in various types of cancer; therapeutic strategies used by Met-targeted agents in urological cancers are summarized in this review.

  15. Synthesis and Evaluation of Heterocyclic Catechol Mimics as Inhibitors of Catechol-O-methyltransferase (COMT)

    Science.gov (United States)

    2015-01-01

    3-Hydroxy-4-pyridinones and 5-hydroxy-4-pyrimidinones were identified as inhibitors of catechol-O-methyltransferase (COMT) in a high-throughput screen. These heterocyclic catechol mimics exhibit potent inhibition of the enzyme and an improved toxicity profile versus the marketed nitrocatechol inhibitors tolcapone and entacapone. Optimization of the series was aided by X-ray cocrystal structures of the novel inhibitors in complex with COMT and cofactors SAM and Mg2+. The crystal structures suggest a mechanism of inhibition for these heterocyclic inhibitors distinct from previously disclosed COMT inhibitors. PMID:25815153

  16. Association between genes, stressful childhood events and processing bias in depression vulnerable individuals.

    Science.gov (United States)

    Vrijsen, J N; van Oostrom, I; Arias-Vásquez, A; Franke, B; Becker, E S; Speckens, A

    2014-06-01

    The brain-derived neurotrophic factor (BDNF) and catechol-O-methyltransferase (COMT) genes are relevant candidates for depression. Variation in these genes is associated with stress sensitivity and depressotypic cognitive biases. The interaction between genes and stressful events is considered as an important mechanism in the development of depression. This study examined the effects of the BDNF and COMT genes on biased processing and the interaction with childhood stress in vulnerable individuals. A total of 198 remitted depressed individuals performed an n-back task with emotional facial stimuli (happy and sad). Childhood events were measured with a questionnaire. Genotype by childhood events interactions were analyzed for happy and sad expressions for BDNF (Val66Met; rs6265) and COMT (Val158Met; rs4680), individually and combined. BDNF and COMT both interacted significantly (P = 0.006 and P = 0.014, respectively) with childhood trauma on reaction time for happy faces. For both genes, Met-carriers with childhood trauma showed less positive bias for happy faces than those without childhood trauma. Val-carriers did not show a differential bias. Individuals with childhood trauma and 3 or 4 risk alleles (BDNF and COMT combined) showed less positive bias than those without childhood trauma (P = 0.011). The BDNF × COMT × childhood trauma interaction yielded a P = 0.055, but had limited power. A potential weakness is the measurement method of the childhood events, as negative bias might have affected participants' recall. Our findings endorse the association of BDNF and COMT with stress and depression and provide a possible intermediate, i.e. biased processing of positive information. Tailoring treatment to specific risk profiles based on genetic susceptibility and childhood stress could be promising. © 2014 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  17. Associations of Cigarette Smoking and Polymorphisms in Brain-Derived Neurotrophic Factor and Catechol-O-Methyltransferase with Neurocognition in Alcohol Dependent Individuals during Early Abstinence

    Directory of Open Access Journals (Sweden)

    Timothy eDurazzo

    2012-10-01

    Full Text Available Chronic cigarette smoking and polymorphisms in brain-derived neurotrophic factor (BDNF and catechol-o-methyltransferase (COMT are associated with neurocognition in normal controls and those with various neuropsychiatric conditions. The influence of these polymorphisms on neurocognition in alcohol dependence is unclear. The goal of this report was to investigate the associations of single nucleotide polymorphisms (SNP in BDNF Val66Met and COMT Val158Met with neurocognition in a treatment-seeking alcohol dependent cohort and determine if neurocognitive differences between non-smokers and smokers previously observed in this cohort persist when controlled for these functional SNPs. Genotyping was conducted on 70 primarily male treatment-seeking alcohol dependent participants (ALC who completed a comprehensive neuropsychological battery after 33 ± 9 days of monitored abstinence. Smoking ALC performed significantly worse than non-smoking ALC on the domains of auditory-verbal and visuospatial learning and memory, cognitive efficiency, general intelligence, processing speed and global neurocognition. In smoking ALC, greater number of years of smoking over lifetime was related to poorer performance on multiple domains. COMT Met homozygotes were superior to Val homozygotes on measures of executive skills and showed trends for higher general intelligence and visuospatial skills, while COMT Val/Met heterozygotes showed significantly better general intelligence than Val homozygotes. COMT Val homozygotes performed better than heterozygotes on auditory-verbal memory. BDNF genotype was not related to any neurocognitive domain. The findings are consistent with studies in normal controls and neuropsychiatric cohorts that observed COMT Met carriers showed better performance on measures of executive skills and general intelligence. Overall, the findings support to the expanding clinical movement to make smoking cessation programs available at the inception of

  18. Nisine geholpen met hordentechnologie

    NARCIS (Netherlands)

    Jong, de L.S.

    2001-01-01

    Een combinatie van nisine met carvacrol, thymol of carvon leidde tot een synergistische reductie van het aantal levensvatbare cellen van Listeria monocytogenes en Bacillus cereus. Verslag van een promotieonderzoek

  19. Sterren scoren met airbag

    NARCIS (Netherlands)

    Slütter, M.

    2010-01-01

    De praktijktest voor het airbagsysteem voor fietsers begint deze maand in Den Haag en Utrecht. Autofabrikanten hebben nu al interesse getoond. Dat is niet verwonderlijk, want met deze airbag kunnen ze sterren verdienen in de botsproeven van EuroNCAP.

  20. Zuinig met antibiotica

    NARCIS (Netherlands)

    Kuipers, A.; Wemmenhove, H.

    2011-01-01

    Het antibioticagebruik op melkveebedrijven is in beeld gebracht. Hoe benutten we deze gegevens om zuiniger met antibiotica om te gaan en hoe denken dierenartsen hierop in te spelen? Speelt de keuze voor verschillende middelen een rol?

  1. When Historiography Met Epistemology

    Directory of Open Access Journals (Sweden)

    Jean-François Stoffel

    2017-06-01

    Full Text Available Review of Bordoni, Stefano. When historiography met epistemology: Sophisticated histories and philosophies of science in French-speaking countries in the second half of the nineteenth century. Reviewed by Jean-François Stoffel.

  2. Genetic vs. pharmacological inactivation of COMT influences cannabinoid-induced expression of schizophrenia-related phenotypes.

    Science.gov (United States)

    O'Tuathaigh, Colm M P; Clarke, Gerard; Walsh, Jeremy; Desbonnet, Lieve; Petit, Emilie; O'Leary, Claire; Tighe, Orna; Clarke, Niamh; Karayiorgou, Maria; Gogos, Joseph A; Dinan, Ted G; Cryan, John F; Waddington, John L

    2012-10-01

    Catechol-O-methyltransferase (COMT) is an important enzyme in the metabolism of dopamine and disturbance in dopamine function is proposed to be central to the pathogenesis of schizophrenia. Clinical epidemiological studies have indicated cannabis use to confer a 2-fold increase in risk for subsequent onset of psychosis, with adolescent-onset use conveying even higher risk. There is evidence that a high activity COMT polymorphism moderates the effects of adolescent exposure to cannabis on risk for adult psychosis. In this paper we compared the effect of chronic adolescent exposure to the cannabinoid WIN 55212 on sensorimotor gating, behaviours related to the negative symptoms of schizophrenia, anxiety- and stress-related behaviours, as well as ex-vivo brain dopamine and serotonin levels, in COMT KO vs. wild-type (WT) mice. Additionally, we examined the effect of pretreatment with the COMT inhibitor tolcapone on acute effects of this cannabinoid on sensorimotor gating in C57BL/6 mice. COMT KO mice were shown to be more vulnerable than WT to the disruptive effects of adolescent cannabinoid treatment on prepulse inhibition (PPI). Acute pharmacological inhibition of COMT in C57BL/6 mice also modified acute cannabinoid effects on startle reactivity, as well as PPI, indicating that chronic and acute loss of COMT can produce dissociable effects on the behavioural effects of cannabinoids. COMT KO mice also demonstrated differential effects of adolescent cannabinoid administration on sociability and anxiety-related behaviour, both confirming and extending earlier reports of COMT×cannabinoid effects on the expression of schizophrenia-related endophenotypes.

  3. Modification of COMT-dependent pain sensitivity by psychological stress and sex.

    Science.gov (United States)

    Meloto, Carolina B; Bortsov, Andrey V; Bair, Eric; Helgeson, Erika; Ostrom, Cara; Smith, Shad B; Dubner, Ronald; Slade, Gary D; Fillingim, Roger B; Greenspan, Joel D; Ohrbach, Richard; Maixner, William; McLean, Samuel A; Diatchenko, Luda

    2016-04-01

    Catecholamine-O-methyltransferase (COMT) is a polymorphic gene whose variants affect enzymatic activity and pain sensitivity via adrenergic pathways. Although COMT represents one of the most studied genes in human pain genetics, findings regarding its association with pain phenotypes are not always replicated. Here, we investigated if interactions among functional COMT haplotypes, stress, and sex can modify the effect of COMT genetic variants on pain sensitivity. We tested these interactions in a cross-sectional study, including 2 cohorts, one of 2972 subjects tested for thermal pain sensitivity (Orofacial Pain: Prospective Evaluation and Risk Assessment) and one of 948 subjects with clinical acute pain after motor vehicle collision (post-motor vehicle collision). In both cohorts, the COMT high-pain sensitivity (HPS) haplotype showed robust interaction with stress and number of copies of the HPS haplotype was positively associated with pain sensitivity in nonstressed individuals, but not in stressed individuals. In the post-motor vehicle collision cohort, there was additional modification by sex: the HPS-stress interaction was apparent in males, but not in females. In summary, our findings indicate that stress and sex should be evaluated in association studies aiming to investigate the effect of COMT genetic variants on pain sensitivity.

  4. Rekenen met vercijferde data

    NARCIS (Netherlands)

    Veugen, P.J.M.

    2011-01-01

    Een nieuwe techniek om bestaande en nieuwe toepassingen ‘privacy vriendelijk’ te maken is gebaseerd op het concept ‘rekenen met vercijferde data’. In dit artikel wordt dit mysterieuze idee uit de doeken gedaan en wordt de kracht ervan duidelijk gemaakt.

  5. BacMet

    DEFF Research Database (Denmark)

    Pal, Chandan; Bengtsson-Palme, Johan; Rensing, Christopher Günther T;

    2014-01-01

    -selection. Information on metal and biocide resistance genes, including their sequences and molecular functions, is, however, scattered. Here, we introduce BacMet (http://bacmet.biomedicine.gu.se) - a manually curated database of antibacterial biocide- and metal-resistance genes based on an in-depth review...

  6. Pionieren met informeel overleg

    NARCIS (Netherlands)

    Doornbos, N.

    2012-01-01

    Conflicthanteringspalet’, ‘escalatieladder’, ‘keukentafelgesprek’… Het zogenoemde pioniersproject van het Ministerie van Binnenlandse Zaken en Koninkrijksrelaties ‘Prettig contact met de overheid’ heeft de woordenschat aardig wat aangevuld. Zelfs de term LSD krijgt een nieuwe inhoud: luisteren - sam

  7. Pionieren met informeel overleg

    NARCIS (Netherlands)

    Doornbos, N.

    2012-01-01

    Conflicthanteringspalet’, ‘escalatieladder’, ‘keukentafelgesprek’… Het zogenoemde pioniersproject van het Ministerie van Binnenlandse Zaken en Koninkrijksrelaties ‘Prettig contact met de overheid’ heeft de woordenschat aardig wat aangevuld. Zelfs de term LSD krijgt een nieuwe inhoud: luisteren -

  8. Mechanische onkruidbestrijding met perspectief

    NARCIS (Netherlands)

    Bleeker, P.O.

    2011-01-01

    Intra-rijwieders met schoffels, lichtsensoren en camera’s: deze intelligente machines bestrijden het onkruid in de gewasrij mechanisch. Ze zijn ontwikkeld voor de biologische landbouw. De sensoren en camera’s bepalen de plaats van het gewas, waarna de schoffels per rij het onkruid tussen de planten

  9. Pionieren met informeel overleg

    NARCIS (Netherlands)

    Doornbos, N.

    2012-01-01

    Conflicthanteringspalet’, ‘escalatieladder’, ‘keukentafelgesprek’… Het zogenoemde pioniersproject van het Ministerie van Binnenlandse Zaken en Koninkrijksrelaties ‘Prettig contact met de overheid’ heeft de woordenschat aardig wat aangevuld. Zelfs de term LSD krijgt een nieuwe inhoud: luisteren - sam

  10. Auguste Comte's blunder: an account of the first century of stellar spectroscopy and how it took one hundred years to prove that Comte was wrong!

    Science.gov (United States)

    Hearnshaw, John

    2010-07-01

    In 1835 the French philosopher Auguste Comte predicted that we would never know anything about the chemical composition of stars. This paper gives a broad overview of the development of stellar spectroscopy, especially from about 1860. Developments in stellar spectroscopy segregated quite clearly into three main fields of endeavour: spectral classification, radial velocities and spectral analysis. This paper concentrates mainly on spectral analysis, or how stellar spectroscopy one hundred years after Comte showed that quantitative information on the composition of stars was possible. The journey was quite arduous, as it required numerous developments in theoretical physics and in laboratory spectroscopy, which in turn allowed stellar spectral analysis successfully to be undertaken by the mid-twentieth century. The key developments in physics that first had to be understood were in quantum and atomic theory, ionization theory, the concept of the Planck function, local thermodynamic equilibrium, the first stellar model atmospheres, line formation theory, turbulence, collisional broadening of spectral lines and the theory of radiative transfer and of the curve of growth. The close links between stellar spectroscopy and theoretical physics will be emphasized. In addition laboratory physics, to measure line wavelengths and oscillator strengths, was also an essential precursor to quantitative data on the chemical composition of stars. Comte may have been an influential philosopher of science in his time. Perhaps his one small transgression was not to have read the works of Joseph Fraunhofer, which in the early nineteenth century already contained the first small clues that Comte's assertion might be wrong.

  11. Estimation of the sanitary impact associated to the domestic exposure to radon in Franche-Comte; Estimation de l'impact sanitaire associe a l'exposition domestique au radon en Franche-Comte

    Energy Technology Data Exchange (ETDEWEB)

    Catelinois, O.; Pirard, P. [Institut de Veille Sanitaire, Saint-Maurice (France); Clinard, F.; Aury, K.; Tillier, C. [Cire Centre-Est, 21 - Dijon (France); Aury, K. [Registre Dijonnais des AVC, Centre d' Epidemiologie de Population, 21 - Dijon (France); Noury, L. [Direction Regionale des Affaires Sanitaires et Sociales de Franche-Comte, 25 - Besancon (France); Hochard, A. [Observatoire Regional de la Sante de Franche-Comte, 25 - Besancon (France)

    2008-09-15

    The importance of the impact of public health associate to domestic radon exposure in Franche-Comte is clearly formulated. The radon concentrations are higher in the granite areas. However, the impact is essentially concentrated in the Franche-Comte sedimentary areas where the essential of the population lives. (N.C.)

  12. Low enzymatic activity haplotypes of the human catechol-O-methyltransferase gene: enrichment for marker SNPs.

    Directory of Open Access Journals (Sweden)

    Andrea G Nackley

    Full Text Available Catechol-O-methyltransferase (COMT is an enzyme that plays a key role in the modulation of catechol-dependent functions such as cognition, cardiovascular function, and pain processing. Three common haplotypes of the human COMT gene, divergent in two synonymous and one nonsynonymous (val(158met position, designated as low (LPS, average (APS, and high pain sensitive (HPS, are associated with experimental pain sensitivity and risk of developing chronic musculoskeletal pain conditions. APS and HPS haplotypes produce significant functional effects, coding for 3- and 20-fold reductions in COMT enzymatic activity, respectively. In the present study, we investigated whether additional minor single nucleotide polymorphisms (SNPs, accruing in 1 to 5% of the population, situated in the COMT transcript region contribute to haplotype-dependent enzymatic activity. Computer analysis of COMT ESTs showed that one synonymous minor SNP (rs769224 is linked to the APS haplotype and three minor SNPs (two synonymous: rs6267, rs740602 and one nonsynonymous: rs8192488 are linked to the HPS haplotype. Results from in silico and in vitro experiments revealed that inclusion of allelic variants of these minor SNPs in APS or HPS haplotypes did not modify COMT function at the level of mRNA folding, RNA transcription, protein translation, or enzymatic activity. These data suggest that neutral variants are carried with APS and HPS haplotypes, while the high activity LPS haplotype displays less linked variation. Thus, both minor synonymous and nonsynonymous SNPs in the coding region are markers of functional APS and HPS haplotypes rather than independent contributors to COMT activity.

  13. Catechol-O-methyltransferase Val(108/158)Met polymorphism affects fronto-limbic connectivity during emotional processing in bipolar disorder.

    Science.gov (United States)

    Vai, B; Riberto, M; Poletti, S; Bollettini, I; Lorenzi, C; Colombo, C; Benedetti, F

    2016-12-30

    Catechol-O-methyltransferase (COMT) inactivates catecholamines, Val/Val genotype was associated to an increased amygdala (Amy) response to negative stimuli and can influence the symptoms severity and the outcome of bipolar disorder, probably mediated by the COMT polymorphism (rs4680) interaction between cortical and subcortical dopaminergic neurotransmission. The aim of this study is to explore how rs4680 and implicit emotional processing of negative emotional stimuli could interact in affecting the Amy connectivity in bipolar depression. Forty-five BD patients (34 Met carriers vs. 11 Val/Val) underwent fMRI scanning during implicit processing of fearful and angry faces. We explore the effect of rs4680 on the strength of functional connectivity from the amygdalae to whole brain. Val/Val and Met carriers significantly differed for the connectivity between Amy and dorsolateral prefrontal cortex (DLPFC) and supramarginal gyrus. Val/Val patients showed a significant positive connectivity for all of these areas, where Met carriers presented a significant negative one for the connection between DLPFC and Amy. Our findings reveal a COMT genotype-dependent difference in corticolimbic connectivity during affective regulation, possibly identifying a neurobiological underpinning of clinical and prognostic outcome of BD. Specifically, a worse antidepressant recovery and clinical outcome previously detected in Val/Val patients could be associated to a specific increased sensitivity to negative emotional stimuli.

  14. Conscientiousness is modified by genetic variation in catechol-O-methyltransferase to reduce symptom complaints in IBS patients

    Science.gov (United States)

    Hall, Kathryn T; Tolkin, Benjamin R; Chinn, Garrett M; Kirsch, Irving; Kelley, John M; Lembo, Anthony J; Kaptchuk, Ted J; Kokkotou, Efi; Davis, Roger B; Conboy, Lisa A

    2015-01-01

    Background Attention to and perception of physical sensations and somatic states can significantly influence reporting of complaints and symptoms in the context of clinical care and randomized trials. Although anxiety and high neuroticism are known to increase the frequency and severity of complaints, it is not known if other personality dimensions or genes associated with cognitive function or sympathetic tone can influence complaints. Genetic variation in catechol-O-methyltransferase (COMT) is associated with anxiety, personality, pain, and response to placebo treatment. We hypothesized that the association of complaint reporting with personality might be modified by variation in the COMT val158met genotype. Methods We administered a standard 25-item complaint survey weekly over 3-weeks to a convenience sample of 187 irritable bowel syndrome patients enrolled in a placebo intervention trial and conducted a repeated measures analysis. Results We found that complaint severity rating, our primary outcome, was negatively associated with the personality measures of conscientiousness (β = −0.31 SE 0.11, P = 0.003) and agreeableness (β = −0.38 SE 0.12, P = 0.002) and was positively associated with neuroticism (β = 0.24 SE 0.09, P = 0.005) and anxiety (β = 0.48 SE 0.09, P < 0.0001). We also found a significant interaction effect of COMT met alleles (β = −32.5 SE 14.1, P = 0.021). in patients genotyped for COMT val158met (N  = 87) specifically COMT × conscientiousness (β = 0.73 SE 0.26, P = 0.0042) and COMT × anxiety (β = −0.42 SE 0.16, P = 0.0078) interaction effects. Conclusion These findings potentially broaden our understanding of the factors underlying clinical complaints to include the personality dimension of conscientiousness and its modification by COMT. PMID:25722948

  15. Metsään.fi-metsäsuunnitelma OTSO Metsäpalveluissa

    OpenAIRE

    Karimo, Jussi

    2016-01-01

    Opinnäytetyön lähtökohtana oli OTSO Metsäpalveluiden halu kehittää Metsään.fi-palvelusta saatavan tiedon perusteella tehtävä metsäsuunnitelmatuote. Metsäsuunnitelmatuotteella tarkoitettiin uudenlaista metsäsuunnitelmaa, joka tehtäisiin Metsään.fi-palvelun tietoa hyödyntäen. Opinnäytetyön tarkoituksena oli kartoittaa OTSOn metsäpalveluhenkilöstön näkemyksiä Metsään.fi-palvelusta, jotta selviäisi, kannattaako heidän mielestään Metsään.fi-palvelua hyödyntää metsäsuunnitelmatyökaluna. Lisäksi hal...

  16. The Role of Catechol-O-Methyltransferase (COMT Gene in the Etiopathogenesis of Schizophrenia

    Directory of Open Access Journals (Sweden)

    Ceren Acar

    2014-09-01

    Full Text Available Genetic factors in the risk of developing schizophrenia is of great importance. With the help of the advances in the field of genetics in recent years by using linkage analysis several genes have been identified that may be a risk factor in schizophrenia. Several association studies have been performed in many different populations on the candidate susceptibility genes that were defined in previous studies. However, these studies give controversial results in different countries with different populations, and there are problems in obtaining replicable results. In this review we aimed to focus on the genetic basis of schizophrenia and the relationship between schizophrenia and catechol-O-methyltransferase (COMT gene. COMT encodes an enzyme molecule which has an important function in dopamine pathways. It has great importance in catecholamine metabolism and pharmacology and genetic mechanism of catechol metabolism variations and their clinical consequences. COMT transfers the methyl group from S-adenosyl-methionine to the hydroxyl group of catechol nucleus (such as dopamine, norepinephrine or catechol estrogen. Genetic variations found in COMT gene are associated with a broad spectrum of clinical phenotype including psychiatric disorders or estrogen related cancers. Several groups have performed studies on the relationship between schizophrenia and COMT. The most commonly studied polymorphism in COMT gene is rs4680 and it causes a valine methionine conversion at codon 158. The association studies on this polymorphism in different populations gave both positive and negative results. Schizoprenia is a complex disease caused by the interaction of environmental and genetic factors, while interpreting the genetic data, this fact and the possibility of the presence of different gene products should be taken into account. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(3.000: 217-226

  17. TPMT, COMT and ACYP2 genetic variants in paediatric cancer patients with cisplatin-induced ototoxicity.

    Science.gov (United States)

    Thiesen, Signe; Yin, Peng; Jorgensen, Andrea L; Zhang, Jieying Eunice; Manzo, Valentina; McEvoy, Laurence; Barton, Christopher; Picton, Susan; Bailey, Simon; Brock, Penelope; Vyas, Harish; Walker, David; Makin, Guy; Bandi, Srinivas; Pizer, Barry; Hawcutt, Daniel B; Pirmohamed, Munir

    2017-06-01

    Cisplatin ototoxicity affects 42-88% of treated children. Catechol-O-methyltransferase (COMT), thiopurine methyltransferase (TPMT) and AYCP2 genetic variants have been associated with ototoxicity, but the findings have been contradictory. The aims of the study were as follows: (a) to investigate these associations in a carefully phenotyped cohort of UK children and (b) to perform a systematic review and meta-analysis. We recruited 149 children from seven UK centres using a retrospective cohort study design. All participants were clinically phenotyped carefully. Genotyping was performed for one ACYP2 (rs1872328), three TPMT (rs12201199, rs1142345 and rs1800460) and two COMT (rs4646316 and rs9332377) variants. For CTCAE grading, hearing loss was present in 91/120 (75.8%; worst ear) and 79/120 (65.8%; better ear). Using Chang grading, hearing loss was diagnosed in 85/119 (71.4%; worst ear) versus 75/119 (63.0%; better ear). No TPMT or COMT single-nucleotide polymorphisms (SNPs) were associated with ototoxicity. ACYP2 SNP rs1872328 was associated with ototoxicity (P=0.027; worst ear). Meta-analysis of our data with that reported in previous studies showed the pooled odds ratio (OR) to be statistically significant for both the COMT SNP rs4646316 (OR: 1.50; 95% confidence interval: 1.15-1.95) and the ACYP2 SNP rs1872328 (OR: 5.91; 95% confidence interval: 1.51-23.16). We showed an association between the ACYP2 polymorphism and cisplatin-induced ototoxicity, but not with the TPMT and COMT. A meta-analysis was statistically significant for both the COMT rs4646316 and the ACYP2 rs1872328 SNPs. Grading the hearing of children with asymmetric hearing loss requires additional clarification.

  18. Cognitive manic symptoms in bipolar disorder associated with polymorphisms in the DAOA and COMT genes.

    Directory of Open Access Journals (Sweden)

    Dzana Sudic Hukic

    Full Text Available INTRODUCTION: Bipolar disorder is characterized by severe mood symptoms including major depressive and manic episodes. During manic episodes, many patients show cognitive dysfunction. Dopamine and glutamate are important for cognitive processing, thus the COMT and DAOA genes that modulate the expression of these neurotransmitters are of interest for studies of cognitive function. METHODOLOGY: Focusing on the most severe episode of mania, a factor was found with the combined symptoms of talkativeness, distractibility, and thought disorder, considered a cognitive manic symptoms (CMS factor. 488 patients were genotyped, out of which 373 (76% had talkativeness, 269 (55% distractibility, and 372 (76% thought disorder. 215 (44% patients were positive for all three symptoms, thus showing CMS (Table 1. As population controls, 1,044 anonymous blood donors (ABD were used. Case-case and case-control design models were used to investigate genetic associations between cognitive manic symptoms in bipolar 1 disorder and SNPs in the COMT and DAOA genes. [Table: see text]. RESULTS: The finding of this study was that cognitive manic symptoms in patients with bipolar 1 disorder was associated with genetic variants in the DAOA and COMT genes. Nominal association for DAOA SNPs and COMT SNPs to cognitive symptoms factor in bipolar 1 disorder was found in both allelic (Table 2 and haplotypic (Table 3 analyses. Genotypic association analyses also supported our findings. However, only one association, when CMS patients were compared to ABD controls, survived correction for multiple testing by max (T permutation. Data also suggested interaction between SNPs rs2391191 in DAOA and rs5993883 in COMT in the case-control model. [Table: see text] [Table: see text]. CONCLUSION: Identifying genes associated with cognitive functioning has clinical implications for assessment of prognosis and progression. Our finding are consistent with other studies showing genetic associations

  19. Time Course Field Analysis of COMT-Downregulated Switchgrass: Lignification, Recalcitrance, and Rust Susceptibility

    Energy Technology Data Exchange (ETDEWEB)

    Baxter, Holly L.; Mazarei, Mitra; Fu, Chunxiang; Cheng, Qunkang; Turner, Geoffrey B.; Sykes, Robert W.; Windham, Mark T.; Davis, Mark F.; Dixon, Richard A.; Wang, Zeng-Yu; Stewart, C. Neal

    2016-05-18

    Modifying plant cell walls by manipulating lignin biosynthesis can improve biofuel yields from lignocellulosic crops. For example, transgenic switchgrass lines with downregulated expression of caffeic acid O-methyltransferase, a lignin biosynthetic enzyme, produce up to 38% more ethanol than controls. The aim of the present study was to understand cell wall lignification over the second and third growing seasons of COMT-downregulated field-grown switchgrass. COMT gene expression, lignification, and cell wall recalcitrance were assayed for two independent transgenic lines at monthly intervals. Switchgrass rust (Puccinia emaculata) incidence was also tracked across the seasons. Trends in lignification over time differed between the 2 years. In 2012, sampling was initiated in mid-growing season on reproductive-stage plants and there was little variation in the lignin content of all lines (COMT-downregulated and control) over time. COMT-downregulated lines maintained 11-16% less lignin, 33-40% lower S/G (syringyl-to-guaiacyl) ratios, and 15-42% higher sugar release relative to controls for all time points. In 2013, sampling was initiated earlier in the season on elongation-stage plants and the lignin content of all lines steadily increased over time, while sugar release expectedly decreased. S/G ratios increased in non-transgenic control plants as biomass accumulated over the season, while remaining relatively stable across the season in the COMT-downregulated lines. Differences in cell wall chemistry between transgenic and non-transgenic lines were not apparent until plants transitioned to reproductive growth in mid-season, after which the cell walls of COMT-downregulated plants exhibited phenotypes consistent with what was observed in 2012. There were no differences in rust damage between transgenics and controls at any time point. These results provide relevant fundamental insights into the process of lignification in a maturing field-grown biofuel feedstock with

  20. Right secondary somatosensory cortex-a promising novel target for the treatment of drug-resistant neuropathic orofacial pain with repetitive transcranial magnetic stimulation.

    Science.gov (United States)

    Lindholm, Pauliina; Lamusuo, Salla; Taiminen, Tero; Pesonen, Ullamari; Lahti, Ari; Virtanen, Arja; Forssell, Heli; Hietala, Jarmo; Hagelberg, Nora; Pertovaara, Antti; Parkkola, Riitta; Jääskeläinen, Satu

    2015-07-01

    High-frequency repetitive transcranial magnetic stimulation (rTMS) of the motor cortex has analgesic effect; however, the efficacy of other cortical targets and the mode of action remain unclear. We examined the effects of rTMS in neuropathic orofacial pain, and compared 2 cortical targets against placebo. Furthermore, as dopaminergic mechanisms modulate pain responses, we assessed the influence of the functional DRD2 gene polymorphism (957C>T) and the catechol-O-methyltransferase (COMT) Val158Met polymorphism on the analgesic effect of rTMS. Sixteen patients with chronic drug-resistant neuropathic orofacial pain participated in this randomized, placebo-controlled, crossover study. Navigated high-frequency rTMS was given to the sensorimotor (S1/M1) and the right secondary somatosensory (S2) cortices. All subjects were genotyped for the DRD2 957C>T and COMT Val158Met polymorphisms. Pain, mood, and quality of life were monitored throughout the study. The numerical rating scale pain scores were significantly lower after the S2 stimulation than after the S1/M1 (P = 0.0071) or the sham (P = 0.0187) stimulations. The Brief Pain Inventory scores were also lower 3 to 5 days after the S2 stimulation than those at pretreatment baseline (P = 0.0127 for the intensity of pain and P = 0.0074 for the interference of pain) or after the S1/M1 (P = 0.001 and P = 0.0001) and sham (P = 0.0491 and P = 0.0359) stimulations. No correlations were found between the genetic polymorphisms and the analgesic effect in the present small clinical sample. The right S2 cortex is a promising new target for the treatment of neuropathic orofacial pain with high-frequency rTMS.

  1. Variation in the dopamine D2 receptor gene plays a key role in human pain and its modulation by transcranial magnetic stimulation.

    Science.gov (United States)

    Jääskeläinen, Satu K; Lindholm, Pauliina; Valmunen, Tanja; Pesonen, Ullamari; Taiminen, Tero; Virtanen, Arja; Lamusuo, Salla; Forssell, Heli; Hagelberg, Nora; Hietala, Jarmo; Pertovaara, Antti

    2014-10-01

    We tested whether variation of the dopamine D2 receptor (DRD2) gene contributes to individual differences in thermal pain sensitivity and analgesic efficacy of repetitive transcranial magnetic stimulation (rTMS) in healthy subjects (n=29) or susceptibility to neuropathic pain in patients with neurophysiologically confirmed diagnosis (n=16). Thermal sensitivity of healthy subjects was assessed before and after navigated rTMS provided to the S1/M1 cortex. All subjects were genotyped for the DRD2 gene 957C>T and catechol-O-methyltransferase (COMT) protein Val158Met polymorphisms. In healthy subjects, 957C>T influenced both innocuous and noxious thermal detection thresholds that were lowest in 957TT homozygotes (P values from .0277 to .0462). rTMS to S1 cortex had analgesic effect only in 957TT homozygote genotype (P=.0086). In patients, prevalence of 957TT homozygote genotype was higher than in a healthy Finnish population (50% vs 27%; P=.0191). Patients with 957TT genotype reported more severe pain than patients with other genotypes (P=.0351). COMT Val158Met polymorphism was not independently associated with the studied variables. Genetic regulation of DRD2 function by 957C>T polymorphism thus seems to influence thermal and pain sensitivity, its modulation by rTMS, and susceptibility to neuropathic pain. This indicates a central role for the dopamine system and DRD2 in pain and analgesia. This may have clinical implications regarding individualized selection of patients for rTMS treatment and assessment of risks for neuropathic pain.

  2. Synthesis and optimization of N-heterocyclic pyridinones as catechol-O-methyltransferase (COMT) inhibitors.

    Science.gov (United States)

    Zhao, Zhijian; Harrison, Scott T; Schubert, Jeffrey W; Sanders, John M; Polsky-Fisher, Stacey; Zhang, Nanyan Rena; McLoughlin, Debra; Gibson, Christopher R; Robinson, Ronald G; Sachs, Nancy A; Kandebo, Monika; Yao, Lihang; Smith, Sean M; Hutson, Pete H; Wolkenberg, Scott E; Barrow, James C

    2016-06-15

    A series of N-heterocyclic pyridinone catechol-O-methyltransferase (COMT) inhibitors were synthesized. Physicochemical properties, including ligand lipophilic efficiency (LLE) and clogP, were used to guide compound design and attempt to improve inhibitor pharmacokinetics. Incorporation of heterocyclic central rings provided improvements in physicochemical parameters but did not significantly reduce in vitro or in vivo clearance. Nevertheless, compound 11 was identified as a potent inhibitor with sufficient in vivo exposure to significantly affect the dopamine metabolites homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC), and indicate central COMT inhibition.

  3. La metáfora

    DEFF Research Database (Denmark)

    Agustin, Oscar Garcia

    2007-01-01

    La función de la metáfora ha sido revisada desde distintas disciplinas. Desde la hermenéutica, se destaca la naturaleza tensional de la metáfora y el modo en que contribuye a crear significaciones nuevas, que rehacen los órdenes semánticos preexistentes. Desde el cognitivismo, la metáfora...

  4. Genetic influences on insight problem solving: the role of catechol-O-methyltransferase (COMT) gene polymorphisms.

    Science.gov (United States)

    Jiang, Weili; Shang, Siyuan; Su, Yanjie

    2015-01-01

    People may experience an "aha" moment, when suddenly realizing a solution of a puzzling problem. This experience is called insight problem solving. Several findings suggest that catecholamine-related genes may contribute to insight problem solving, among which the catechol-O-methyltransferase (COMT) gene is the most promising candidate. The current study examined 753 healthy individuals to determine the associations between 7 candidate single nucleotide polymorphisms on the COMT gene and insight problem-solving performance, while considering gender differences. The results showed that individuals carrying A allele of rs4680 or T allele of rs4633 scored significantly higher on insight problem-solving tasks, and the COMT gene rs5993883 combined with gender interacted with correct solutions of insight problems, specifically showing that this gene only influenced insight problem-solving performance in males. This study presents the first investigation of the genetic impact on insight problem solving and provides evidence that highlights the role that the COMT gene plays in insight problem solving.

  5. A Genetic Variant (COMT) Coding Dopaminergic Activity Predicts Personality Traits in Healthy Elderly.

    Science.gov (United States)

    Kotyuk, Eszter; Duchek, Janet; Head, Denise; Szekely, Anna; Goate, Alison M; Balota, David A

    2015-08-01

    Association studies between the NEO five factor personality inventory and COMT rs4680 have focused on young adults and the results have been inconsistent. However, personality and cortical changes with age may put older adults in a more sensitive range for detecting a relationship. The present study examined associations of COMT rs4680 and personality in older adults. Genetic association analyses were carried out between the NEO and the targeted COMT rs4680 in a large, well-characterized sample of healthy, cognitively normal older adults (N = 616, mean age = 69.26 years). Three significant associations were found: participants with GG genotype showed lower mean scores on Neuroticism (p = 0.039) and higher scores on Agreeableness (p = 0.020) and Conscientiousness (p = 0.006) than participants with AA or AG genotypes. These results suggest that older adults with higher COMT enzymatic activity (GG), therefore lower dopamine level, have lower Neuroticism scores, and higher Agreeableness and Conscientiousness scores. This is consistent with a recent model of phasic and tonic dopamine release suggesting that even though GG genotype is associated with lower tonic dopamine release, the phasic release of dopamine might be optimal for a more adaptive personality profile.

  6. Genetic influences on insight problem solving: The role of catechol-o-methyltransferase (COMT gene polymorphisms

    Directory of Open Access Journals (Sweden)

    Weili eJiang

    2015-10-01

    Full Text Available People may experience an aha moment, when suddenly realizing a solution of a puzzling problem. This experience is called insight problem solving. Several findings suggest that catecholamine-related genes may contribute to insight problem solving, among which the catechol-o-methyltransferase (COMT gene is the most promising candidate. The current study examined 753 healthy individuals to determine the associations between 7 candidate single nucleotide polymorphisms on the COMT gene and insight problem-solving performance, while considering gender differences. The results showed that individuals carrying A allele of rs4680 or T allele of rs4633 scored significantly higher on insight problem-solving tasks, and the COMT gene rs5993883 combined with gender interacted with correct solutions of insight problems, specifically showing that this gene only influenced insight problem-solving performance in males. This study presents the first investigation of the genetic impact on insight problem solving and provides evidence that highlights the role that the COMT gene plays in insight problem solving.

  7. [Five Franche-Comté doctors and surgeons during the Revolution, Empire and the Restoration].

    Science.gov (United States)

    Antoine, Henri-Michel; Magnin, Pierre; Maurat, Jean-Pierre

    2007-01-01

    Five doctors played an important part in medicine in Franche-Comté and more generally speaking in France, during the French Revolution, Empire and Restauration: J.F. Desault, E. Tourtelle, P.F. Percy, J.F. Thomassin and P.F. Briot.

  8. SbCOMT (Bmr12) is involved in the biosynthesis of tricin-lignin in sorghum.

    Science.gov (United States)

    Eudes, Aymerick; Dutta, Tanmoy; Deng, Kai; Jacquet, Nicolas; Sinha, Anagh; Benites, Veronica T; Baidoo, Edward E K; Richel, Aurore; Sattler, Scott E; Northen, Trent R; Singh, Seema; Simmons, Blake A; Loqué, Dominique

    2017-01-01

    Lignin in plant biomass represents a target for engineering strategies towards the development of a sustainable bioeconomy. In addition to the conventional lignin monomers, namely p-coumaryl, coniferyl and sinapyl alcohols, tricin has been shown to be part of the native lignin polymer in certain monocot species. Because tricin is considered to initiate the polymerization of lignin chains, elucidating its biosynthesis and mechanism of export to the cell wall constitute novel challenges for the engineering of bioenergy crops. Late steps of tricin biosynthesis require two methylation reactions involving the pathway intermediate selgin. It has recently been demonstrated in rice and maize that caffeate O-methyltransferase (COMT) involved in the synthesis syringyl (S) lignin units derived from sinapyl alcohol also participates in the synthesis of tricin in planta. In this work, we validate in sorghum (Sorghum bicolor L.) that the O-methyltransferase responsible for the production of S lignin units (SbCOMT / Bmr12) is also involved in the synthesis of lignin-linked tricin. In particular, we show that biomass from the sorghum bmr12 mutant contains lower level of tricin incorporated into lignin, and that SbCOMT can methylate the tricin precursors luteolin and selgin. Our genetic and biochemical data point toward a general mechanism whereby COMT is involved in the synthesis of both tricin and S lignin units.

  9. COMT Diplotype Amplifies Effect of Stress on Risk of Temporomandibular Pain.

    Science.gov (United States)

    Slade, G D; Sanders, A E; Ohrbach, R; Bair, E; Maixner, W; Greenspan, J D; Fillingim, R B; Smith, S; Diatchenko, L

    2015-09-01

    When measured once, psychological stress predicts development of painful temporomandibular disorder (TMD). However, a single measurement fails to characterize the dynamic nature of stress over time. Moreover, effects of stress on pain likely vary according to biological susceptibility. We hypothesized that temporal escalation in stress exacerbates risk for TMD, and the effect is amplified by allelic variants in a gene, catechol-O-methyltransferase (COMT), regulating catechol neurotransmitter catabolism. We used data from the Orofacial Pain: Prospective Evaluation and Risk Assessment prospective cohort study of 2,707 community-dwelling adults with no lifetime history of TMD on enrollment. At baseline and quarterly periods thereafter, the Perceived Stress Scale (PSS) measured psychological stress. Genotyped DNA from blood samples determined COMT diplotypes. During follow-up of 0.25 to 5.2 y, 248 adults developed examiner-verified incident TMD. PSS scores at baseline were 20% greater (P developed incident TMD compared with TMD-free controls. Baseline PSS scores increased by 9% (P = 0.003) during follow-up in cases but remained stable in controls. This stress escalation was limited to incident cases with COMT diplotypes coding for low-activity COMT, signifying impaired catabolism of catecholamines. Cox regression models confirmed significant effects on TMD hazard of both baseline PSS (P < 0.001), modeled as a time-constant covariate, and change in PSS (P < 0.001), modeled as a time-varying covariate. Furthermore, a significant (P = 0.04) interaction of COMT diplotype and time-varying stress showed that a postbaseline increase of 1.0 standard deviation in PSS more than doubled risk of TMD incidence in subjects with low-activity COMT diplotypes (hazard ratio = 2.35; 95% confidence limits: 1.66, 3.32), an effect not found in subjects with high-activity COMT diplotypes (hazard ratio = 1.42; 95% confidence limits: 0.96, 2.09). Findings provide novel insights into dynamic

  10. Delayed O-methylation of l-DOPA in MB-COMT-deficient mice after oral administration of l-DOPA and carbidopa.

    Science.gov (United States)

    Tammimäki, Anne; Aonurm-Helm, Anu; Männistö, Pekka T

    2017-04-21

    1. Catechol-O-methyltransferase (COMT) is involved in the O-methylation of l-DOPA, dopamine, and other catechols. The enzyme is expressed in two isoforms: soluble (S-COMT), which resides in the cytoplasm, and membrane-bound (MB-COMT), which is anchored to intracellular membranes. 2. To obtain specific information on the functions of COMT isoforms, we studied how a complete MB-COMT deficiency affects the total COMT activity in the body, peripheral l-DOPA levels, and metabolism after l-DOPA (10 mg kg(-1)) plus carbidopa (30 mg kg(-1)) administration by gastric tube in wild-type (WT) and MB-COMT-deficient mice. l-DOPA and 3-O-methyl-l-DOPA (3-OMD) levels were assayed in plasma, duodenum, and liver. 3. We showed that the selective lack of MB-COMT did not alter the total COMT activity, COMT enzyme kinetics, l-DOPA levels, or the total O-methylation of l-DOPA but delayed production of 3-OMD in plasma and peripheral tissues.

  11. Vroegtijdig Phytophthora opsporen met biosensor

    NARCIS (Netherlands)

    Jansen, R.M.C.

    2003-01-01

    Phytophthora kan vroegtijdig worden opgespoord met biosensoren. Bij de Leerstoelgroep Agrarische Bedrijfstechnologie van Wageningen Universiteit wordt verder gekeken naar praktische toepassingen van deze techniek

  12. Dopamine genes and reward dependence in adolescents with excessive internet video game play.

    Science.gov (United States)

    Han, Doug Hyun; Lee, Young Sik; Yang, Kevin C; Kim, Eun Young; Lyoo, In Kyoon; Renshaw, Perry F

    2007-09-01

    Excessive internet video game play (EIGP) has emerged as a leading cause of behavioral and developmental problems in adolescents. Recent research has implicated the role of striatal dopaminergic system in the behavioral maladaptations associated with EIGP. This study investigates the reward-dependence characteristics in EIGP adolescents as it potentially relates to genetic polymorphisms of the dopaminergic system and temperament. Seventy-nine male EIGP adolescents and 75 age- and gender-matched healthy comparison adolescents were recruited. Associations were tested with respect to the reward-dependence (RD) scale in Cloninger's Temperament and Character Inventory and the frequencies of 3 dopamine polymorphisms: Taq1A1 allele of the dopamine D2 receptor (DRD2 Taq1A1) and Val158Met in the Catecholamine-O-Methyltransferase (COMT) genes. The Taq1A1 and low activity (COMT) alleles were significantly more prevalent in the EIGP group relative to the comparison group. The present EIGP group had significantly higher RD scores than controls. Within the EIGP group, the presence of the Taq1A1 allele correlated with higher RD scores. Our findings suggest that EIGP subjects have higher reward dependency and an increased prevalence of the DRD2 Taq1A1 and COMT alleles. In particular, the DRD2 Taq1A1 allele seems to be associated with reward dependence in EIGP adolescents.

  13. The COMTval158met polymorphism is associated with symptom relief during exposure-based cognitive-behavioral treatment in panic disorder

    Directory of Open Access Journals (Sweden)

    Bergström Jan

    2010-11-01

    Full Text Available Abstract Background Cognitive behavioral therapy (CBT represents a learning process leading to symptom relief and resulting in long-term changes in behavior. CBT for panic disorder is based on exposure and exposure-based processes can be studied in the laboratory as extinction of experimentally acquired fear responses. We have recently demonstrated that the ability to extinguish learned fear responses is associated with a functional genetic polymorphism (COMTval158met in the COMT gene and this study was aimed at transferring the experimental results on the COMTval158met polymorphism on extinction into a clinical setting. Methods We tested a possible effect of the COMTval158met polymorphism on the efficacy of CBT, in particular exposure-based treatment modules, in a sample of 69 panic disorder patients. Results We present evidence that panic patients with the COMTval158met met/met genotype may profit less from (exposure-based CBT treatment methods as compared to patients carrying at least one val-allele. No association was found with the 5-HTTLPR/rs25531 genotypes which is presented as additional material. Conclusions We were thus able to transfer findings on the effect of the COMTval158met polymorphism from an experimental extinction study obtained using healthy subjects to a clinical setting. Furthermore patients carrying a COMT val-allele tend to report more anxiety and more depression symptoms as compared to those with the met/met genotype. Limitations of the study as well as possible clinical implications are discussed. Trial registration Clinical Trial Registry name: Internet-Versus Group-Administered Cognitive Behavior Therapy for Panic Disorder (IP2. Registration Identification number: NCT00845260, http://www.clinicaltrials.gov/ct2/show/NCT00845260

  14. Sexually dimorphic effects of catechol-O-methyltransferase (COMT inhibition on dopamine metabolism in multiple brain regions.

    Directory of Open Access Journals (Sweden)

    Linda M Laatikainen

    Full Text Available The catechol-O-methyltransferase (COMT enzyme metabolises catecholamines. COMT inhibitors are licensed for the adjunctive treatment of Parkinson's disease and are attractive therapeutic candidates for other neuropsychiatric conditions. COMT regulates dopamine levels in the prefrontal cortex (PFC but plays a lesser role in the striatum. However, its significance in other brain regions is largely unknown, despite its links with a broad range of behavioural phenotypes hinting at more widespread effects. Here, we investigated the effect of acute systemic administration of the brain-penetrant COMT inhibitor tolcapone on tissue levels of dopamine, noradrenaline, and the dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC and homovanillic acid (HVA. We examined PFC, striatum, hippocampus and cerebellum in the rat. We studied both males and females, given sexual dimorphisms in several aspects of COMT's function. Compared with vehicle, tolcapone significantly increased dopamine levels in the ventral hippocampus, but did not affect dopamine in other regions, nor noradrenaline in any region investigated. Tolcapone increased DOPAC and/or decreased HVA in all brain regions studied. Notably, several of the changes in DOPAC and HVA, particularly those in PFC, were more prominent in females than males. These data demonstrate that COMT alters ventral hippocampal dopamine levels, as well as regulating dopamine metabolism in all brain regions studied. They demonstrate that COMT is of significance beyond the PFC, consistent with its links with a broad range of behavioural phenotypes. Furthermore, they suggest that the impact of tolcapone may be greater in females than males, a finding which may be of clinical significance in terms of the efficacy and dosing of COMT inhibitors.

  15. Microbewerking met behulp van lasers

    NARCIS (Netherlands)

    Ezendam, M.M.M.

    1994-01-01

    Het bewerken van materialen met behulp van lasers staat momenteel enorm in de belangstelling, en terecht. De ontwikkeling van bestaande en nieuwe typen lasers staat alles behalve stil. Ontwikkelingen bevinden zich met name in het gebied van hogere vermogens, betere bundelkwaliteit en hogere

  16. A influência do positivismo de Augusto Comte no Partenon Literário

    Directory of Open Access Journals (Sweden)

    Paulo Gilberto Mossmann Sobrinho

    2010-10-01

    Full Text Available O artigo discute as influências do positivismo de Auguste Comte entre os membros da Sociedade do Partenon Literário, apresentando uma lacuna encontrada na historiografia gaúcha que sugere a propagação das ideias positivistas no Rio Grande do Sul através da citada agremiação, sem, contudo, apresentar de forma significativa de que modo o positivismo influenciou os intelectuais atuantes nessa sociedade.

  17. Comte, Mach, Planck, and Eddington: a study of influence across generations

    Science.gov (United States)

    Batten, Alan H.

    2016-04-01

    Auguste Comte is frequently ridiculed by astronomers for saying that human beings would never be able to know the physical nature and constitution of the stars. His philosophy, however, influenced scientists throughout his lifetime and for over a century after his death. That influence is traced here in the work of three outstanding scientists who spanned, roughly speaking, three successive generations after his own, namely, Ernst Mach, Max Planck and Arthur Stanley Eddington.

  18. Impact of DRD2/ANKK1 and COMT Polymorphisms on Attention and Cognitive Functions in Schizophrenia

    Science.gov (United States)

    Breton, Florence; Mallet, Jasmina; Gorwood, Philip; Dubertret, Caroline

    2017-01-01

    Background Cognitive deficits such as poor selective attention and executive functions decline have been reported in patients with schizophrenia. Many studies have emphasized the role of dopamine in regulating cognitive functions in the general population as well as in schizophrenia. However, the relationship between cognitive processes, schizophrenia and dopaminergic candidate genes is an original approach given interesting results. The purpose of the current exploratory study was to examine the interaction of dopaminergic genes (coding for dopamine receptor D2, DRD2, and for Catecholamine-O-Methyl-Transferase, COMT) with the diagnostic of schizophrenia in (i) the executive control of attention, (ii) selective attention, and (iii) executive functions. Methods and Results We recruited 52 patients with schizophrenia and 53 healthy controls who performed the Stroop Color-Word Test, the Attention Network Test and the Wisconsin Card Sorting test. Four single nucleotide polymorphisms (SNPs) in the DRD2 gene (rs6275, rs6277, rs2242592 and rs1800497) and two SNPs in the COMT gene (rs4680 and rs165599) have been genotyped. Patients with schizophrenia performed significantly worse than controls in all cognitive performance, taking into account demographic variables. A significant gene by disease interaction was found for the Stroop interference (p = 0.002) for rs6275 of the DRD2 gene. The COMT Val/Val genotype and schizophrenia were associated with increased number of perseverative errors (p = 0.01). Conclusions In our study, the DRD2 gene is involved in attention while the COMT gene is implicated in executive functions in patients with schizophrenia. PMID:28085950

  19. Influence of catechol-O-methyltransferase (COMT) gene polymorphisms in pain sensibility of Brazilian fibromialgia patients.

    Science.gov (United States)

    Barbosa, Flávia Regina; Matsuda, Josie Budag; Mazucato, Mendelson; de Castro França, Suzelei; Zingaretti, Sônia Marli; da Silva, Lucienir Maria; Martinez-Rossi, Nilce Maria; Júnior, Milton Faria; Marins, Mozart; Fachin, Ana Lúcia

    2012-02-01

    Fibromyalgia syndrome (FS) is a rheumatic syndrome affecting to 2-3% of individuals of productive age, mainly women. Neuroendocrine and genetic factors may play a significant role in development of the disease which is characterized by diffuse chronic pain and presence of tender points. Several studies have suggested an association between FS, especially pain sensitivity, and polymorphism of the catechol-O-methyltransferase (COMT) gene. The aim of the present study was to characterize the SNPs rs4680 and rs4818 of the COMT gene and assess its influence in pain sensitivity of patients with fibromyalgia screened by the Fibromyalgia Impact Questionnaire (FIQ). DNA was extracted from peripheral blood of 112 patients with fibromyalgia and 110 healthy individuals and was used as template in PCR for amplification of a 185-bp fragment of the COMT gene. The amplified fragment was sequenced for analyses of the SNPs rs4680 and rs4818. The frequency of mutant genotype AA of SNP rs6860 was 77.67% in patients with FS and 28.18% for the control group. For the SNP rs4818, the frequency of mutant genotype CC was 73.21 and 39.09% for patients with FS and controls, respectively. Moreover, the FIQ score was higher in patients with the homozygous mutant genotype for SNPs rs4680 (87.92 points) and rs4818 (86.14 points). These results suggest that SNPs rs4680 and rs4818 of the COMT gene may be associated with fibromyalgia and pain sensitivity in FS Brazilian patients.

  20. Genetic variation in catechol-O-methyltransferase (COMT) and obesity in the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial.

    Science.gov (United States)

    Wang, Sophia S; Morton, Lindsay M; Bergen, Andrew W; Lan, Elizabeth Z; Chatterjee, Nilanjan; Kvale, Paul; Hayes, Richard B; Chanock, Stephen J; Caporaso, Neil E

    2007-08-01

    Catechol-O-methyltransferase (COMT) is an important modulator in the catabolism of extraneural dopamine, which plays an important role in drug reward mechanisms. It is hypothesized that genetic variations in the COMT gene, which can result in a three to fourfold difference in COMT enzyme activity, may be associated with several reward-motivated behaviors. The aim of our study was to examine the relationship between COMT polymorphisms with smoking, obesity and alcohol. Three single nucleotide polymorphisms (SNPs) in COMT were genotyped in 2,371 participants selected randomly from the screening arm of the PLCO Cancer Screening Trial after stratifying by sex, age, and smoking status. Smoking, obesity, and alcohol consumption were assessed by questionnaire. SNP and haplotype associations were estimated using odds ratios (ORs) and 95% confidence intervals (CIs) derived from conditional logistic regression models, adjusted for race/ethnicity. The COMT Ex4-76C > G (Leu136Leu) polymorphism was statistically significantly associated with individuals who had >30% increases in BMI from ages 20 to 50 years, compared to those with 0-5% increase in BMI (0-5%) over the same age period: (CC is referent; OR(CG )= 1.42, OR(GG )= 1.46, P (trend )= 0.06). By sex, the increased risk was further pronounced among females (OR(CG )= 1.50, OR(GG )= 2.10, P (trend )= 0.03). Consistent with our analyses of single polymorphisms, individuals whose BMI increased >30% from ages 20 to 50 years were more likely than individuals with 0-5% increases in BMI to possess COMT haplotypes [COMT Ex3-104C > T-COMT Ex4-76 C > G-COMT Ex4-12 A > G] that included the variant allele for COMT Ex4-76 C > G: C-G-G (T-C-A is referent: OR(C-G-G )= 1.33, 95% CI 1.01-1.77) and C-G-A (OR(C-G-A )= 1.79, 95% CI 0.72-4.49). We observed no association between any of the COMT polymorphisms with smoking behavior or alcohol intake. The COMT Ex4-76C > G (Leu136Leu) polymorphism appears to play a role in large increases in BMI

  1. Factors affecting cognitive remediation response in schizophrenia: the role of COMT gene and antipsychotic treatment.

    Science.gov (United States)

    Bosia, Marta; Zanoletti, Andrea; Spangaro, Marco; Buonocore, Mariachiara; Bechi, Margherita; Cocchi, Federica; Pirovano, Adele; Lorenzi, Cristina; Bramanti, Placido; Smeraldi, Enrico; Cavallaro, Roberto

    2014-06-30

    Cognitive remediation is the best available tool to treat cognitive deficits in schizophrenia and has evidence of biological validity; however results are still heterogeneous and significant predictors are lacking. Previous studies showed that cognitive remediation is able to induce changes in PFC function and dopaminergic transmission and thus the study of possible sources of variability at these levels (i.e. antipsychotic treatments and genetic variability) might help to gain a deeper understanding of neurobiological correlates and translate into optimization and personalization of interventions. In the present study, we analyzed the interaction between pharmacological treatment (clozapine vs typical/atypical D2 blockers) and COMT rs4680 polymorphism on cognitive changes after cognitive remediation therapy, in a sample of 98 clinically stabilized patients with schizophrenia. The General Linear Model showed a significant interaction of pharmacological treatment and COMT polymorphism on the improvement in "Symbol Coding" subtest, a global measure of speed of processing. Post-hoc analysis revealed a significant difference between COMT genotypes, when treated with D2 blockers, with worse results among Val/Val patients. These preliminary results suggest that genetic variability, influencing prefrontal dopamine, might affect individual capacity to improve with different patterns, depending on antipsychotic treatment.

  2. Gezondheidsrisico's in verband met het werken met Polychloorbifenylen : een onderzoek

    NARCIS (Netherlands)

    Geuskens, R.B.M.; Nossent, S.M.; Koëter, H.B.W.M.; Dreef-van der Meulen, H.C.; Stijkel, A.; Zielhuis, R.L.

    1989-01-01

    Met behulp van gegevens verkregen uit een werkplekinventarisatie naar gegevens over produktie/gebruik, risicopopulatie en (mogelijke) blootstelling aan polychloorbifenylen (PCB's), en een literatuurstudie naar mogelijke schadelijke eigenschappen van PCB's op het reproductiesysteem en/of nageslacht (

  3. El comte Arnau, la migració d’un mite

    Directory of Open Access Journals (Sweden)

    Maria de la Pau Janer Mulet

    2016-06-01

    Full Text Available En aquest article es presenta l’estudi de la figura del comte Arnau, heroi llegendari sorgit a les terres de la Catalunya Vella el drama del qual ha travessat els segles i ha estat difós per mitjà d’una balada i uns textos llegendaris de caràcter oral. El senyor poderós i malvat, sacríleg sense escrúpols i amic del diable, apareix a la seva esposa després de mort, sorgit de l’infern, com una ànima en pena que recorre la terra muntat en un cavall de flames. La balada, en forma de diàleg entre la dama i l’espectre del comte, ens reconta la causa de la seva condemna: «per soldades mal pagades», perquè no pagà els jornals que havia promès als seus treballadors. Per mitjà de la història llegendària del comte Arnau, el poble qüestionava la legitimitat d’un senyor incapaç de complir les seves promeses. En migrar a l’illa de Mallorca, el mite es consolida en un personatge històricament identificat que concentra les malvestats del comte llegendari, desapareix qualsevol al·lusió al tema dels jornals mal pagats, però persisteix en la denúncia d’un comte malvat i dèspota. This article presents the study of the figure of Conde Arnau, the legendary hero from the Old Catalunya lands, whose history has passed through the centuries and has spreaded through a ballad and legendary spoken texts. The powerful and bad master, without scruples and friend of the devil, appears to his wife after death. He comes out of hell, like a spirit in pain, wandering the land on a horse of flames. The ballad was composed in form of a dialogue between the lady and the spirit of the Conde. Through the legendary history of the Conde Arnau, the villagers questioned the legitimity of the Master, who was unable tu fulfelt his promises. In inmigrated to the island of Mallorca, the legend is consolidated in one identified historical character, which was concentrated in this legendary conde badness.

  4. Cahier Welzijnsgids. Omgaan met beroepsgeheim

    Directory of Open Access Journals (Sweden)

    Hilde Vlaeminck

    2016-03-01

    Full Text Available Bernard Hubeau, Jos Mertens, Johan Put, Rudi Roose, Kris Stas, Freya Vander Laenen (Eds.. Cahier Welzijnsgids. Omgaan met beroepsgeheim. Mechelen: Kluwer, 182 p., €31,60. ISBN 978 90 4655 475 3

  5. Compost voor biggen met diarree

    NARCIS (Netherlands)

    Gommers, T.

    1990-01-01

    Het geven van compost aan biggen met diarree zorgt op het Proefstation voor de Varkenshouderij voor minder medicijngebruik. De biggen krijgen de compost van groente-, fruit- en tuinafval vanaf de tweede dag na de geboorte, zodra de diarreeverschijnselen zichtbaar zijn.

  6. Metallurgical Laboratory (MET-LAB)

    Data.gov (United States)

    Federal Laboratory Consortium — The MET-LAB can perform materials characterization for all types of metallic components and systems to any industry-specific or military standard. Capabilities: The...

  7. Catechol-o-methyltransferase gene polymorphism is associated with skeletal muscle properties in older women alone and together with physical activity.

    Directory of Open Access Journals (Sweden)

    Paula H A Ronkainen

    Full Text Available BACKGROUND: Muscle strength declines on average by one percent annually from midlife on. In postmenopausal women this decrement coincides with a rapid decline in estrogen production. The genetics underlying the effects of estrogen on skeletal muscle remains unclear. In the present study, we examined whether polymorphisms within COMT and ESR1 are associated with muscle properties and assessed their interaction and their combined effects with physical activity. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional data analysis was conducted with 434 63-76-year-old women from the population-based Finnish Twin Study on Aging. Body anthropometry, muscle cross-sectional area (mCSA, isometric hand grip and knee extension strengths, and leg extension power were measured. COMT Val158Met and ESR1 PvuII genotypes were determined by the RFLP method. mCSA differed by COMT genotypes (p = 0.014 being significantly larger in LL than HL individuals in unadjusted (p = 0.001 and age- and height-adjusted model (p = 0.004. When physical activity and age were entered into GEE model, COMT genotype had a significant main effect (p = 0.038 on mCSA. Furthermore, sedentary individuals with the HH genotype had lower muscle mass, strength and power, but they also appeared to benefit the most from physical activity. No association of ESR1 PvuII polymorphism with any of the muscle outcomes was observed. CONCLUSIONS/SIGNIFICANCE: The present study suggests that the COMT polymorphism, affecting the activity of the enzyme, is associated with muscle mass. Furthermore, sedentary individuals with potential high enzyme activity were the weakest group, but they may potentially benefit the most from physical activity. This observation elucidates the importance of both environmental and genetic factors in muscle properties.

  8. Augusto Comte y sus discípulos ortodoxos frente a la cuestión colonial

    Directory of Open Access Journals (Sweden)

    Tonatiuh Useche Sandoval

    2015-01-01

    Full Text Available Este artículo presenta la oposición de Augusto Comte y sus discípulos al movimiento colonizador que emanó del Occidente europeo durante el siglo XIX. Aunque considera Europa como el centro de la Humanidad, Comte sostiene que la contribución europea al progreso de los pueblos menos avanzados no reside en la dominación colonial, sino en la difusión pacífica de una doctrina demostrable. En un primer momento se resume la apreciación globalmente negativa de Comte sobre la colonización moderna; luego se evocan sus propuestas para valorar a los colonizados y combatir los argumentos colonialistas; finalmente se toma el caso de la conquista francesa de Argelia para comparar la posición de Comte con la de Tocqueville y la de Enfantin. En un segundo momento se subraya la influencia moral que sus discípulos ejercieron en Inglaterra en contra de la colonización exterior. Se insiste después en el papel significativo que jugaron sus discípulos brasileros en contra de la colonización interior y en pro de la protección de los indígenas. Se concluye que el positivismo de Comte constituye una forma de eurocentrismo anticolonial.

  9. Rapportage gewasbescherming 2007 Telen met toekomst - Bloembollen

    NARCIS (Netherlands)

    Haan, de J.J.

    2008-01-01

    Dit is het vierde rapportage gewasbescherming van het praktijknetwerk Telen met toekomst voor de open teelten. Het praktijknetwerk Telen met toekomst organiseert groepen praktijkbedrijven met hun relaties rond de ontwikkeling van meer duurzame productiesystemen (milieutechnisch, ecologisch en

  10. Association of single nucleotide polymorphisms of ABCB1, OPRM1 and COMT with pain perception in cancer patients.

    Science.gov (United States)

    Wang, Xu-shi; Song, Hai-bin; Chen, Si; Zhang, Wei; Liu, Jia-qi; Huang, Chao; Wang, Hao-ran; Chen, Yuan; Chu, Qian

    2015-10-01

    Pain perception is influenced by multiple factors. The single nucleotide polymorphisms (SNPs) of some genes were found associated with pain perception. This study aimed to examine the association of the genotypes of ABCB1 C3435T, OPRM1 A118G and COMT V108/158M (valine 108/158 methionine) with pain perception in cancer patients. We genotyped 146 cancer pain patients and 139 cancer patients without pain for ABCB1 C3435T (rs1045642), OPRM1 A118G (rs1799971) and COMT V108/158M (rs4680) by the fluorescent dye-terminator cycle sequencing method, and compared the genotype distribution between groups with different pain intensities by chi-square test and pain scores between groups with different genotypes by non-parametric test. The results showed that in these cancer patients, the frequency of variant T allele of ABCB1 C3435T was 40.5%; that of G allele of OPRM1 A118G was 38.5% and that of A allele of COMT V108/158M was 23.3%. No significant difference in the genotype distribution of ABCB1 C3435T (rs1045642) and OPRM1 A118G (rs1799971) was observed between cancer pain group and control group (P=0.364 and 0.578); however, significant difference occurred in the genotype distribution of COMT V108/158M (rs4680) between the two groups (P=0.001). And the difference could not be explained by any other confounding factors. Moreover, we found that the genotypes of COMT V108/158M and ABCB1 C3435T were associated with the intensities of pain in cancer patients. In conclusion, our results indicate that the SNPs of COMT V108/158M and ABCB1 C3435T significantly influence the pain perception in Chinese cancer patients.

  11. COMT and MAO-A polymorphisms and obsessive-compulsive disorder: a family-based association study.

    Directory of Open Access Journals (Sweden)

    Aline Santos Sampaio

    Full Text Available Obsessive-compulsive disorder (OCD is a common and debilitating psychiatric illness. Although a genetic component contributes to its etiology, no single gene or mechanism has been identified to the OCD susceptibility. The catechol-O-methyltransferase (COMT and monoamine oxidase A (MAO-A genes have been investigated in previous OCD studies, but the results are still unclear. More recently, Taylor (2013 in a comprehensive meta-analysis of genetic association studies has identified COMT and MAO-A polymorphisms involved with OCD. In an effort to clarify the role of these two genes in OCD vulnerability, a family-based association investigation was performed as an alternative strategy to the classical case-control design.Transmission disequilibrium analyses were performed after genotyping 13 single-nucleotide polymorphisms (eight in COMT and five in MAO-A in 783 OCD trios (probands and their parents. Four different OCD phenotypes (from narrow to broad OCD definitions and a SNP x SNP epistasis were also analyzed.OCD, broad and narrow phenotypes,were not associated with any of the investigated COMT and MAO-A polymorphisms. In addition, the analyses of gene-gene interaction did not show significant epistatic influences on phenotype between COMT and MAO-A.The findings do not support an association between DSM-IV OCD and the variants of COMT or MAO-A. However, results from this study cannot exclude the contribution of these genes in the manifestation of OCD. The evaluation of broader spectrum phenotypes could help to understand the role of these and other genes in the pathophysiology of OCD and its spectrum disorders.

  12. Biopsychosocial Influence on Exercise-induced Delayed Onset Muscle Soreness at the Shoulder: Pain Catastrophizing and Catechol-O-Methyltransferase (COMT) Diplotype Predict Pain Ratings

    Science.gov (United States)

    George, Steven Z.; Dover, Geoffrey C.; Wallace, Margaret R.; Sack, Brandon K.; Herbstman, Deborah M.; Aydog, Ece; Fillingim, Roger B.

    2009-01-01

    Objective The experience of pain is believed to be influenced by psychologic and genetic factors. A previous study suggested pain catastrophizing and catechol-O-methyltransferase (COMT) genotype influenced clinical pain ratings for patients seeking operative treatment of shoulder pain. This study investigated whether these same psychologic and genetic factors predicted responses to induced shoulder pain. Methods Participants (n=63) completed self-report questionnaires and had COMT genotype determined before performing a standardized fatigue protocol to induce delayed onset muscle soreness. Then, shoulder pain ratings, self-report of upper-extremity disability ratings, and muscle torque production were reassessed 24, 48, and 72 hours later. Results This cohort consisted of 35 women and 28 men, with a mean age of 20.9 years (SD=1.7). The frequency of COMT diplotypes was 42 with “high COMT enzyme activity” (low pain sensitivity group) and 21 with “low COMT enzyme activity” (average pain sensitivity/high pain sensitivity group). A hierarchical regression model indicated that an interaction between pain catastrophizing and COMT diplotype was the strongest unique predictor of 72-hour pain ratings. The same interaction was not predictive of self-report of disability or muscle torque production at 72 hours. The pain catastrophizing × COMT diplotype interaction indicated that participants with high pain catastrophizing and low COMT enzyme activity (average pain sensitivity/high pain sensitivity group) were more likely (relative risk=3.5, P=0.025) to have elevated pain intensity ratings (40/100 or higher). Discussion These findings from an experimental model converge with those from a surgical cohort and provide additional evidence that the presence of elevated pain catastrophizing and COMT diplotype indicative of low COMT enzyme activity have the potential to increase the risk of developing chronic pain syndromes. PMID:18936597

  13. Polymorphisms of serotonin receptor 2A and 2C genes and COMT in relation to obesity and type 2 diabetes

    DEFF Research Database (Denmark)

    Kring, Sofia I I; Werge, Thomas; Holst, Claus

    2009-01-01

    BACKGROUND: Candidate genes of psychological importance include 5HT2A, 5HT2C, and COMT, implicated in the serotonin, noradrenaline and dopamine pathways, which also may be involved in regulation of energy balance. We investigated the associations of single nucleotide polymorphisms (SNPs) of these......BACKGROUND: Candidate genes of psychological importance include 5HT2A, 5HT2C, and COMT, implicated in the serotonin, noradrenaline and dopamine pathways, which also may be involved in regulation of energy balance. We investigated the associations of single nucleotide polymorphisms (SNPs...

  14. Leven met Inflammatory Bowel Disease

    NARCIS (Netherlands)

    Duijvendijk J. van, [No Value

    2004-01-01

    Leven met Inflammatory Bowel Disease Inflammatory bowel disease (IBD) is de verzamelnaam voor Colitis ulcerosa en de ziekte van Crohn. Het zijn chronische darmontstekingen, waarvan de ziekteactiviteit wisselt en zich niet laat voorspellen. Door de lichamelijke klachten en het onvoorspelbare karakter

  15. Water zuiveren met drijvende planten

    NARCIS (Netherlands)

    Keizer-Vlek, H.E.; Verdonschot, P.F.M.; Verdonschot, R.C.M.; Dekkers, T.B.M.

    2013-01-01

    Drijvende moerassystemen met helofyten, ook wel floating treatment wetlands of floatlands genoemd, worden in Nederland uitsluitend toegepast om natuurbeleving te stimuleren en de biodiversiteit van het oppervlaktewater te vergroten. Floatlands zijn echter mogelijk ook geschikt om nutriënten uit het

  16. Fijnstof te lijf met koolzaadolie

    NARCIS (Netherlands)

    Ogink, N.W.M.

    2010-01-01

    Wageningen UR Livestock Research onderzoekt een reeks aan maatregelen die de uitstoot van fijnstof bij pluimveebedrijven kunnen verminderen. Iedere dag wat koolzaadolie vernevelen is tot nu toe het meest hoopgevend, met als bijkomend voordeel dat het stalklimaat verbetert voor mens en dier.

  17. Water zuiveren met drijvende planten

    OpenAIRE

    Keizer-Vlek, H.E.; Verdonschot, P. F. M.; Verdonschot, R.C.M.; Dekkers, T.B.M.

    2013-01-01

    Drijvende moerassystemen met helofyten, ook wel floating treatment wetlands of floatlands genoemd, worden in Nederland uitsluitend toegepast om natuurbeleving te stimuleren en de biodiversiteit van het oppervlaktewater te vergroten. Floatlands zijn echter mogelijk ook geschikt om nutriënten uit het oppervlaktewater te verwijderen. Vooral in het stedelijk gebied is dit een aantrekkelijke optie. De gele lis is er uitermate voor geschikt.

  18. Leven met Inflammatory Bowel Disease

    NARCIS (Netherlands)

    Duijvendijk J. van, [No Value

    2004-01-01

    Leven met Inflammatory Bowel Disease Inflammatory bowel disease (IBD) is de verzamelnaam voor Colitis ulcerosa en de ziekte van Crohn. Het zijn chronische darmontstekingen, waarvan de ziekteactiviteit wisselt en zich niet laat voorspellen. Door de lichamelijke klachten en het onvoorspelbare karakter

  19. Steeds preciezer met de sensor

    NARCIS (Netherlands)

    Houweling, van P.; PPO Akkerbouw, Groene Ruimte en Vollegrondsgroente

    2014-01-01

    Maurits Bax uit Luyksgestel werkt met de Yara N-sensor. Zo spuit hij minder dan een derde van de voorgeschreven dosering voor loofdodingsmiddel in aardappelen. Andere toepassingen zijn minder praktijkrijp, zoals aardappelen bijmesten. Daarvoor lijkt een app, ontwikkeld door het PPO, uitkomst te gaan

  20. Mogelijkheden voor notenteelt met tussengewas

    NARCIS (Netherlands)

    Oosterbaan, A.; Schepers, H.

    2005-01-01

    Er zijn enkele presentaties gehouden over de ervaringen met de teelt van walnoten in Nederland tijdens het vijfde Internationale Walnotencongres in Sorrento, Italië, gehouden in november 2004. De productie van walnoten in Nederland stelt nog niet veel voor. Er is dus ruimte voor eigen productie

  1. The Role of Catechol-O-Methyl Transferase Val(108/158)Met Polymorphism (rs4680) in the Effect of Green Tea on Resting Energy Expenditure and Fat Oxidation: A Pilot Study

    Science.gov (United States)

    Hursel, Rick; Janssens, Pilou L. H. R.; Bouwman, Freek G.; Mariman, Edwin C.; Westerterp-Plantenga, Margriet S.

    2014-01-01

    Introduction Green tea(GT) is able to increase energy expenditure(EE) and fat oxidation(FATox) via inhibition of catechol-O-methyl transferase(COMT) by catechins. However, this does not always appear unanimously because of large inter-individual variability. This may be explained by different alleles of the functional COMT Val108/158Met polymorphism that are associated with COMT enzyme activity; high-activity enzyme, COMTH(Val/Val genotype), and low-activity COMTL(Met/Met genotype). Methods Fourteen Caucasian subjects (BMI: 22.2±2.3 kg/m2, age: 21.4±2.2 years) of whom 7 with the COMTH-genotype and 7 with the COMTL-genotype were included in a randomized, cross-over study in which EE and substrate oxidation were measured with a ventilated-hood system after decaffeinated GT and placebo(PL) consumption. Results At baseline, EE, RQ, FATox and carbohydrate oxidation(CHOox) did not differ between groups. Significant interactions were observed between COMT genotypes and treatment for RQ, FATox and CHOox (p<0.05). After GT vs. PL, EE(GT: 62.2 vs. PL: 35.4 kJ.3.5 hrs; p<0.01), RQ(GT: 0.80 vs. PL: 0.83; p<0.01), FATox(GT: 18.3 vs. PL: 15.3 g/d; p<0.001) and CHOox(GT: 18.5 vs. PL: 24.3 g/d; p<0.001) were significantly different for subjects carrying the COMTH genotype, but not for subjects carrying the COMTL genotype (EE, GT: 60.3 vs. PL: 51.7 kJ.3.5 hrs; NS), (RQ, GT: 0.81 vs. PL: 0.81; NS), (FATox, GT: 17.3 vs. PL: 17.0 g/d; NS), (CHOox, GT: 22.1 vs. PL: 21.4 g/d; NS). Conclusion Subjects carrying the COMTH genotype increased energy expenditure and fat-oxidation upon ingestion of green tea catechins vs, placebo, whereas COMTL genotype carriers reacted similarly to GT and PL ingestion. The differences in responses were due to the different responses on PL ingestion, but similar responses to GT ingestion, pointing to different mechanisms. The different alleles of the functional COMT Val108/158Met polymorphism appear to play a role in the inter-individual variability for EE

  2. Gezondheidsrisico's in verband met het werken met Dieldrin : een onderzoek

    OpenAIRE

    Geuskens, R.B.M.; Nossent, S.M.; Koëter, H.B.W.M.; Dreef-van der Meulen, H.C.; Stijkel, A; Zielhuis, R.L.

    1989-01-01

    Op basis van gegevens verkregen uit een oriënterende werkplekinventarisatie naar gegevens over produktie/gebruik, risicopopulatie en (mogelijke) blootstelling aan dieldrin en een literatuurstudie naar mogelijke schadelijke eigenschappen van dieldrin op het reproduktiesysteem en/of nageslacht (6000S-AIST-73/2) is een evaluatie gemaakt van het gezondheidsrisico van werken met dieldrin. Er zijn aanwijzingen voor reproduktierisico's m.b.t. tot blootstelling van volwassenen. Voor vrouwen in de vru...

  3. 儿茶酚氧位甲基转移酶基因与注意缺陷多动障碍患儿认知功能的关联研究%Association study of catechol-O-methyltransferase gene polymorphism and cognitive function in children with attention deficit hyperactivity disorder in China

    Institute of Scientific and Technical Information of China (English)

    钱秋谨; 王玉凤; 杨莉; 刘豫鑫

    2008-01-01

    目的 探讨儿茶酚氧位甲基转移酶(COMT)基因Va1108/158Met(rs4680)多态性对注意缺陷多动障碍(ADHD)患儿认知功能的影响.方法 对203例中国汉族ADHD患儿进行韦氏记忆测查、Stroop测验及数字划消测查,评定记忆力、反应抑制能力和注意力,并检测COMT基因Va1158Met多态性.按照基因型将样本分为高活性基因型组(92例,ValVal)和中低活性基因型组(111例,ValMet和MetMet),比较两组间各项测查结果的异同.结果 高活性基因型组图片分测验[(11.7±3.1)分]和Stroop测验C部分错误数(0个)的成绩好于中低活性基因型组[分别为(10.8±2.9)分和1个;P<0.05~0.01].两组其他方面的差异均无统计学意义.结论 COMT基因Val158Met多态性与ADHD患儿的认知功能中的记忆力、反应抑制能力和注意力相关.%Objective To investigate the association of catechol-O-methyltransferase (COMT) gene Vl108/158Met SNP (rs4680)with cognitive function in children with attention deficit hyperactivity disorder(ADHD) in China. Methods A total of 203 DSM-1V ADHD children of Chinese Hart descent were included, both the data of neuropsychological tests ( Wechsler Memory Scale, Stroop test and cancellationtest) and COMT Val108/158Met genotyping results were obtained. The two-sample t test and Mann-Whitney test were used to compare the average scores between two groups defined by COMT Val158Met genotypes,high-enzymatic activity ( ValVal, n = 92) and mid-low enzymatic activity ( ValMet and MetMet, n = 111 ).Results The children with high-enzymatic activity (ValVal) performed significantly better on some aspects of Wechsler Memory Scale and Stroop test ( picture recall, and part C error number in Stroop test) than those with mid-low enzymatic activity (P <0.05-0.01 ). No statistically significant differences were found between two groups and index in other tests. Conclusion The results suggest that COMT gene Val108/158Met polymorphism may be related to the

  4. A genetic contribution to cooperation: dopamine-relevant genes are associated with social facilitation.

    Science.gov (United States)

    Walter, Nora T; Markett, Sebastian A; Montag, Christian; Reuter, Martin

    2011-01-01

    Social loafing and social facilitation are stable behavioral effects that describe increased or decreased motivation, as well as effort and cooperation in teamwork as opposed to individual working situations. Recent twin studies demonstrate the heritability of cooperative behavior. Brain imaging studies have shown that reciprocity, cooperativeness, and social rewards activate reward processing areas with strong dopaminergic input, such as the ventral striatum. Thus, candidate genes for social behavior are hypothesized to affect dopaminergic neurotransmission. In the present study, we investigated the dopaminergic genetic contribution to social cooperation, especially to social loafing and social facilitation. N = 106 healthy, Caucasian subjects participated in the study and were genotyped for three polymorphisms relevant to the dopaminergic system (COMTval158met, DRD2 c957t, DRD2 rs#2283265). In addition to a main effect indicating an increased performance in teamwork situations, we found a significant interaction between a haplotype block covering both DRD2 single nucleotide polymorphisms (SNPs) (rs#6277 and rs#2283265), henceforth referred to as the DRD2-haplotype block, and the COMT val158met polymorphism (rs#4680) with social facilitation. Carriers of the DRD2 CT-haplotype block and at least one Val-allele showed a greater increase in performance in teamwork settings when compared with carriers of the CT-haplotype block and the Met/Met-genotype. Our results suggest that epistasis between COMTval158met and the two DRD2 SNPs contributes to individual differences in cooperativeness in teamwork settings.

  5. Janus molecule I: dichotomous effects of COMT in neuropathic vs nociceptive pain modalities.

    Science.gov (United States)

    Segall, S K; Maixner, W; Belfer, I; Wiltshire, T; Seltzer, Z; Diatchenko, L

    2012-05-01

    The enzyme catechol-O-methyltransferase (COMT) has been shown to play a critical role in pain perception by regulating levels of epinephrine (Epi) and norepinephrine (NE). Although the key contribution of catecholamines to the perception of pain has been recognized for a long time, there is a clear dichotomy of observations. More than a century of research has demonstrated that increasing adrenergic transmission in the spinal cord decreases pain sensitivity in animals. Equally abundant evidence demonstrates the opposite effect of adrenergic signaling in the peripheral nervous system, where adrenergic signaling increases pain sensitivity. Viewing pain processing within spinal and peripheral compartments and determining the directionality of adrenergic signaling helps clarify the seemingly contradictory findings of the pain modulatory properties of adrenergic receptor agonists and antagonists presented in other reviews. Available evidence suggests that adrenergic signaling contributes to pain phenotypes through α(1/2) and β(2/3) receptors. While stimulation of α(2) adrenergic receptors seems to uniformly produce analgesia, stimulation of α(1) or β receptors produces either analgesic or hyperalgesic effects. Establishing the directionality of adrenergic receptor modulation of pain processing, and related COMT activity in different pain models are needed to bring meaning to recent human molecular genetic findings. This will enable the translation of current findings into meaningful clinical applications such as diagnostic markers and novel therapeutic targets for complex human pain conditions.

  6. La metáfora

    DEFF Research Database (Denmark)

    Agustin, Oscar Garcia

    2007-01-01

    cuestionamiento de la lógica y de las leyes establecidas se corresponde con lo que denominamos autonomía. Así pues, el proceso de autonomía zapatista consiste, por un lado, en la declaración y aplicación de los derechos indígenas y, por otro, en la creación de un sentido alternativo, donde la metáfora juega un...

  7. La metáfora

    DEFF Research Database (Denmark)

    Agustin, Oscar Garcia

    2007-01-01

    cuestionamiento de la lógica y de las leyes establecidas se corresponde con lo que denominamos autonomía. Así pues, el proceso de autonomía zapatista consiste, por un lado, en la declaración y aplicación de los derechos indígenas y, por otro, en la creación de un sentido alternativo, donde la metáfora juega un...

  8. A multicenter case-control study on screening of single nucleotide polymorphisms in estrogen-metabolizing enzymes and susceptibility to uterine leiomyoma in han chinese.

    Science.gov (United States)

    Shen, Yang; Ren, Mu-Lan; Xu, Jie; Xu, Qian; Ding, Yi-Qian; Wu, Zhi-Cong; Zhang, Hai-Bao; Huang, Xian-Xia; Cai, Yun-Lang

    2014-01-01

    Uterine leiomyoma (UL) is an estrogen-responsive benign tumor in the female reproductive system and the main risk of hysterectomy for women. However, gene polymorphism of estrogen-metabolizing enzymes may lead to the different susceptibility to UL. We detected 10 single mucleotide polymorphisms in three key estrogen metabolite enzymes (COMT, CYP1A1, CYP1B1) in a Chinese Han population consisting of 800 patients and 800 healthy women from five different medical centers. The genetic polymorphism of rs3087869 (IVS1+2329C>T) (OR 3.200, 95% CI 1.614-6.345) and rs4680 (Val158Met) (OR 5.675, 95% CI 2.696-11.942) loci on COMT, rs1048943 (Ile462Val) (OR 4.629, 95% CI 2.216-9.672) and rs4646422 (Gly45Asp) (OR 3.240, 95% CI 1.624-6.461) loci on CYP1A1 and rs1065827 (Ala119Ser) (OR 5.635, 95% CI 2.990-10.619) locus on CYP1B1 were the risk factors to UL development and rs1056836 (Leu432Val) (OR 0.188, 95% CI 0.061-0.575) locus on CYB1B1 may be the protective factor to UL. The results provide a theoretical basis for genetic screening and early intervention to UL-susceptible populations.

  9. The Role of Inherited TPMT and COMT Genetic Variation in Cisplatin-induced Ototoxicity in Children with Cancer

    Science.gov (United States)

    Yang, Jun J.; Lim, Joshua Yew-Suang; Huang, Jie; Bass, Johnnie; Wu, Jianrong; Wang, Chong; Fang, Jie; Stewart, Elizabeth; Harstead, Elaine H.; Shuyu, E; Robinson, Giles W.; Evans, William E.; Pappo, Alberto; Zuo, Jian; Relling, Mary V.; Onar-Thomas, Arzu; Gajjar, Amar; Stewart, Clinton F.

    2013-01-01

    Ototoxicity is a debilitating side effect of platinating agents with substantial inter-patient variability. We sought to evaluate the association of TPMT and COMT genetic variations with cisplatin-related hearing damage in the context of frontline pediatric cancer treatment protocols. In 213 children from St. Jude Medulloblastoma-96 and -03 protocols, hearing loss was related to younger age (P=0.013) and craniospinal irradiation (P=0.001), but did not differ by TPMT or COMT variants. Results were similar in an independent cohort of 41 children from solid tumor frontline protocols. Functional hearing loss or hair cell damage was not different in TPMT knockout vs. wildtype mice following cisplatin treatment, and neither TPMT nor COMT variant was associated with cisplatin cytotoxicity in lymphoblastoid cell lines. In conclusion, our results indicated that TPMT or COMT genetic variation was not related to cisplatin ototoxicity in children with cancer and did not influence cisplatin-induced hearing damage in laboratory models. PMID:23820299

  10. The effect of Ecstasy on memory is moderated by a functional polymorphism in the cathechol-O-methyltransferase (COMT) gene

    NARCIS (Netherlands)

    T. Schilt; M.W.J. Koeter; M.M.L. de Win; J.R. Zinkstok; T.A. van Amelsvoort; B. Schmand; W. van den Brink

    2009-01-01

    There is ample evidence for decreased verbal memory in heavy Ecstasy users. However, findings on the presence of a dose-response relation are inconsistent, possibly due to individual differences in genetic vulnerability. Catechol-O-methyltransferase (COMT) is involved in the catabolism of Ecstasy. T

  11. Molecular cloning, characterization and expression of the caffeic acid O-methyltransferase (COMT) ortholog from kenaf (Hibiscus cannabinus)

    Science.gov (United States)

    We cloned the full-length of the gene putatively encoding caffeic acid O-methyltransferase (COMT) from kenaf (Hibiscus cannabinus L.) using degenerate primers and the RACE (rapid amplification of cDNA ends) method. Kenaf is an herbaceous and rapidly growing dicotyledonous plant with great potential ...

  12. The effect of acute moderate psychological stress on working memory-related neural activity is modulated by a genetic variation in catecholaminergic function in humans

    Directory of Open Access Journals (Sweden)

    Shaozheng eQin

    2012-05-01

    Full Text Available Acute stress has an important impact on higher-order cognitive functions supported by the prefrontal cortex (PFC such as working memory (WM. In rodents, such effects are mediated by stress-induced alterations in catecholaminergic signaling, but human data in support of this notion is lacking. A common variation in the gene encoding Catechol-O-methyltransferase (COMT is known to affect basal catecholaminergic availability and PFC functions. Here, we investigated whether this genetic variation (Val158Met modulates effects of stress on WM-related prefrontal activity in humans. In a counterbalanced crossover design, 41 healthy young men underwent functional Magnetic Resonance Imaging (fMRI while performing a numerical N-back WM task embedded in a stressful or neutral context. Moderate psychological stress was induced by a well-controlled procedure involving viewing strongly aversive (versus emotionally neutral movie material in combination with a self-referencing instruction. Acute stress resulted in genotype-dependent effects on WM performance and WM-related activation in the dorsolateral PFC, with a relatively negative impact of stress in COMT Met-homozygotes as opposed to a relatively positive effect in Val-carriers. A parallel interaction was found for WM-related deactivation in the anterior medial temporal lobe. Our findings suggest that individuals with higher baseline catecholaminergic availability (COMT Met-homozygotes appear to reach a supraoptimal state under moderate levels of stress. In contrast, individuals with lower baselines (Val-carriers may reach an optimal state. Thus, our data show that effects of acute stress on higher-order cognitive functions vary depending on catecholaminergic availability at baseline, and thereby corroborate animal models of catecholaminergic signaling that propose a non-linear relationship between catecholaminergic activity and prefrontal functions.

  13. Investigation of polymorphisms in genes involved in estrogen metabolism in menstrual migraine.

    Science.gov (United States)

    Sutherland, Heidi G; Champion, Morgane; Plays, Amelie; Stuart, Shani; Haupt, Larisa M; Frith, Alison; MacGregor, E Anne; Griffiths, Lyn R

    2017-04-05

    Migraine is a common, disabling headache disorder, which is influenced by multiple genes and environmental triggers. After puberty, the prevalence of migraine in women is three times higher than in men and >50% of females suffering from migraine report a menstrual association, suggesting hormonal fluctuations can influence the risk of migraine attacks. It has been hypothesized that the drop in estrogen during menses is an important trigger for menstrual migraine. Catechol-O-methyltransferase (COMT) and Cytochrome P450 (CYP) enzymes are involved in estrogen synthesis and metabolism. Functional polymorphisms in these genes can influence estrogen levels and therefore may be associated with risk of menstrual migraine. In this study we investigated four single nucleotide polymorphisms in three genes involved in estrogen metabolism that have been reported to impact enzyme levels or function, in a specific menstrual migraine cohort. 268 menstrual migraine cases and 142 controls were genotyped for rs4680 in COMT (Val158Met), rs4646903 and rs1048943 in CYP1A1 (T3801C and Ile462Val) and rs700519 in CYP19A1 (Cys264Arg). Neither genotype nor allele frequencies for the COMT and CYP SNPs genotyped were found to be significantly different between menstrual migraineurs and controls by chi-square analysis (P>0.05). Therefore we did not find association of functional polymorphisms in the estrogen metabolism genes COMT, CYP1A1 or CYP19A1 with menstrual migraine. Further studies are required to assess whether menstrual migraine is genetically distinct from the common migraine subtypes and identify genes that influence risk.

  14. Simultaneous MAO-B and COMT inhibition in L-Dopa-treated patients with Parkinson's disease.

    Science.gov (United States)

    Lyytinen, J; Kaakkola, S; Ahtila, S; Tuomainen, P; Teräväinen, H

    1997-07-01

    The effect of selegiline (L-deprenyl) on plasma catecholamines, clinical response, and drug tolerability was studied in 13 patients with Parkinson's disease (PD) treated with L-Dopa/benserazide and entacapone, a peripheral catechol-O-methyltransferase (COMT) inhibitor, in a placebo-controlled double-blind study. An L-Dopa test was performed on 3 study days. The first study day was with L-Dopa/benserazide only (control), the second after 14 days of treatment with 200 mg entacapone taken concomitantly with L-Dopa/benserazide in combination with either selegiline (10 mg daily) or placebo. After a 2-week washout period, selegiline and placebo treatments were switched, and the third study day was after 14 days of treatment. During the study days, clinical response was evaluated at 30-min intervals for 6 h, by using the motor score of the Unified Parkinson's Disease Rating Scale (UPDRS). In addition, repeated blood pressure measurements were made, and plasma samples were taken for analysis of L-Dopa, 3-O-methyldopa (3-OMD), dihydroxyphenyl acetic acid (DOPAC), homovanillic acid (HVA), dopamine, noradrenaline, and 3-methoxy-4-hydroxyphenylethylene glycol (MHPG). Monoamine oxidase B (MAO-B) and COMT enzyme activities were measured from platelets and erythrocytes, respectively. Entacapone improved the clinical response to L-Dopa during both selegiline and placebo (p DOPAC levels and decreased plasma 3-OMD and MHPG levels both with selegiline and placebo. Selegiline partially inhibited the entacapone-induced increase of plasma DOPAC. Plasma dopamine and noradrenaline levels did not change. Entacapone decreased erythrocyte COMT activity by > 35% (p patient withdrew because of diarrhea, dizziness, and loss of sleep when receiving selegiline treatment. Otherwise no differences in adverse events, mean daily blood pressures, or other safety parameters were observed between selegiline and placebo treatments. Our results suggest that entacapone can be safely administered together

  15. Study of traits and recalcitrance reduction of field-grown COMT down-regulated switchgrass

    Energy Technology Data Exchange (ETDEWEB)

    Li, Mi; Pu, Yunqiao; Yoo, Chang Geun; Gjersing, Erica; Decker, Stephen R.; Doeppke, Crissa; Shollenberger, Todd; Tschaplinski, Timothy J.; Engle, Nancy L.; Sykes, Robert W.; Davis, Mark F.; Baxter, Holly L.; Mazarei, Mitra; Fu, Chunxiang; Dixon, Richard A.; Wang, Zeng-Yu; Neal Stewart, C.; Ragauskas, Arthur J.

    2017-01-03

    The native recalcitrance of plants hinders the biomass conversion process using current biorefinery techniques. Down-regulation of the caffeic acid O-methyltransferase (COMT) gene in the lignin biosynthesis pathway of switchgrass reduced the thermochemical and biochemical conversion recalcitrance of biomass. Due to potential environmental influences on lignin biosynthesis and deposition, studying the consequences of physicochemical changes in field-grown plants without pretreatment is essential to evaluate the performance of lignin-altered plants. We determined the chemical composition, cellulose crystallinity and the degree of its polymerization, molecular weight of hemicellulose, and cellulose accessibility of cell walls in order to better understand the fundamental features of why biomass is recalcitrant to conversion without pretreatment. The most important is to investigate whether traits and features are stable in the dynamics of field environmental effects over multiple years.

  16. According to reports of Baron de Bois le Comte, women in Ottoman during Mahmud II.

    Directory of Open Access Journals (Sweden)

    Turgut Subaşı

    2012-06-01

    Full Text Available Women’s place and manner of lives is designated according to Islamic law in Ottoman society. Besides, the manners such as apparel, social rights, getting married and divorced of Ottoman women takes form within the frame of both Islamic law and Turkish culture.In this article, Ottoman women’s status, rights, place in social life, alteration and evolution that have been formed in a particular framework will be conveyed with the French Diplomat Baron de Bois le Comte’s point of view who occupied in the Ottoman Empire in the reign of II. Mahmud. Providing a different perspective for this reign, Baron de Bois le Comte is a diplomat who has been sent by French Foreign Affairs to Ottoman Empire with a “special mission” in order to observe, mediate and solve problems in Ottoman Empire within the time period where Egyptian Crisis which had started with the Revolt of Mehmet Ali Pasa. Baron de Bois le Comte had entered Ottoman Empire through Egypt’s Alexandria and been in several Ottoman Empire cities afterwards. Examining Ottoman Empire in detail, French diplomat reported his observations to French Minister of Foreign Affairs of the period, Mösyö Broglie, on a regular basis.This article will enables us to take a look at the Ottoman women’s status and social life outside home in XIX. Century’s first half which is prepared based on Baron de Bois le Comte’s observations and reports about Ottoman women while he was in the capital city of Ottoman Empire, Istanbul.

  17. According to reports of Baron de Bois le Comte, women in Ottoman during Mahmud II.

    Directory of Open Access Journals (Sweden)

    Turgut Subaşı

    2013-02-01

    Full Text Available Women’s place and manner of lives is designated according to Islamic law in Ottoman society. Besides, the manners such as apparel, social rights, getting married and divorced of Ottoman women takes form within the frame of both Islamic law and Turkish culture. In this article, Ottoman women’s status, rights, place in social life, alteration and evolution that have been formed in a particular framework will be conveyed with the French Diplomat Baron de Bois le Comte’s point of view who occupied in the Ottoman Empire in the reign of II. Mahmud. Providing a different perspective for this reign, Baron de Bois le Comte is a diplomat who has been sent by French Foreign Affairs to Ottoman Empire with a “special mission” in order to observe, mediate and solve problems in Ottoman Empire within the time period where Egyptian Crisis which had started with the Revolt of Mehmet Ali Pasa. Baron de Bois le Comte had entered Ottoman Empire through Egypt’s Alexandria and been in several Ottoman Empire cities afterwards. Examining Ottoman Empire in detail, French diplomat reported his observations to French Minister of Foreign Affairs of the period, Mösyö Broglie, on a regular basis. This article will enables us to take a look at the Ottoman women’s status and social life outside home in XIX. Century’s first half which is prepared based on Baron de Bois le Comte’s observations and reports about Ottoman women while he was in the capital city of Ottoman Empire, Istanbul.

  18. Rapportage gewasbescherming 2007 Telen met toekomst - Champignons

    NARCIS (Netherlands)

    Haan, de J.J.

    2008-01-01

    Het praktijknetwerk Telen met toekomst organiseert groepen praktijkbedrijven met hun relaties rond de ontwikkeling van meer duurzame productiesystemen (milieutechnisch, ecologisch en economisch) in de plantaardige sectoren. Deze rapportage geeft het resultaat van een inventarisatie van de status van

  19. Groepshuisvesting zeugen: brijvoedering met lange trog

    NARCIS (Netherlands)

    Hoofs, A.I.J.; Mheen, van der H.

    2003-01-01

    Brijvoedering via een lange trog combineert de managementvoordelen van gelijktijdig vreten, en stabiele groepen met de economische voordelen van het voeren van brijvoedering met brijproducten. Dit voersysteem geniet dan ook veel belangstelling vanuit de praktijk.

  20. Computergestuurde circulatieregelingen : optimaal bewaarklimaat met minimaal energieverbruik

    NARCIS (Netherlands)

    Wildschut, J.; Janssen, H.J.J.; Sapounas, A.; Gieling, T.H.

    2011-01-01

    Bij het bewaren van bloembollen in kuubskisten gestapeld voor een systeemwand in een bewaarcel wordt voor de ventilatie met buitenlucht, en voor de circulatie met cellucht veel energie verbruikt. Door het ventilatiedebiet met de klimaatcomputer te sturen op basis van ethyleenmeting wordt bij het bew

  1. Role of novelty seeking personality traits as mediator of the association between COMT and onset age of drug use in Chinese heroin dependent patients.

    Directory of Open Access Journals (Sweden)

    Ting Li

    Full Text Available BACKGROUND: Personality traits such as novelty seeking (NS are associated with substance dependence but the mechanism underlying this association remains uncertain. Previous studies have focused on the role of the dopamine pathway. OBJECTIVE: Examine the relationships between allelic variants of the catechol-O-methyltransferase (COMT gene, NS personality traits, and age of onset of drug use in heroin-dependent subjects in China. METHODS: The 478 heroin dependent subjects from four drug rehabilitation centers in Shanghai who were genotyped for eight tagging single nucleotide polymorphisms (SNP on the COMT gene completed the NS subscale from the Temperament and Character Inventory. Multivariate analyses were used to assess the potential mediating role of NS personality traits in the association between COMT gene variants and the age of onset of heroin use. PRINCIPAL FINDINGS AND CONCLUSIONS: In the univariate analysis the COMT rs737866 gene variants were independently associated with both NS and age of onset of drug use: those with the TT genotype had higher NS subscale scores and an earlier onset age of heroin use than individuals with CT or CC genotypes. In the multivariate analysis the inclusion of the NS subscore variable weakened the relationship between the COMT rs737866 TT genotype and an earlier age of onset of drug use. Our findings that COMT is associated with both NS personality traits and with the age of onset of heroin use helps to clarify the complex relationship between genetic and psychological factors in the development of substance abuse.

  2. La posteridad sociológica de Auguste Comte: Lo normal y lo patológico en Durkheim

    Directory of Open Access Journals (Sweden)

    MICHEL BOURDEAU

    2008-01-01

    Full Text Available Este artículo completa un texto que, bajo el título «Ciencia, religión y sociedad en Auguste Comte», fue publicado en el año 2003 en las páginas de esta revista. Después de un breve repaso de los conceptos sociológicos fundamentales del Cours de philosophie positive, se muestra como el pensamiento de Durkheim se constituyó a través de una discusión crítica con el positivismo. Concretamente, se examinan dos momentos fundamentales de dicha confrontación. En primer lugar, se analiza como la distinción que Durkheim establece en La división du travail social (1893 entre solidaridad mecánica y solidaridad orgánica tenía como objetivo fundamental demostrar que Comte se había equivocado al extraer ciertas consecuencias sobre el progreso de la división del trabajo. En segundo lugar, se muestra como en Les Règles de la méthode sociologique (1895, Durkheim atribuye a Comte la distinción entre lo normal y lo patológico y reinterpreta dicha distinción a partir del concepto de «media» de Quételet. En este contexto, concluimos señalando que Durkheim debe a Comte la idea de que la sociología permite construir una ciencia de la moral.

  3. Evidence that COMT genotype and proline interact on negative-symptom outcomes in schizophrenia and bipolar disorder

    OpenAIRE

    Clelland, C L; Drouet, V.; Rilett, K C; Smeed, J A; Nadrich, R H; Rajparia, A; Read, L L; Clelland, J D

    2016-01-01

    Elevated peripheral proline is associated with psychiatric disorders, and there is evidence that proline is a neuromodulator. The proline dehydrogenase (PRODH) gene, which encodes the enzyme that catalyzes proline catabolism, maps to human chromosome 22q11.2, a region conferring risk of schizophrenia. In the Prodh-null mouse, an interaction between elevated peripheral proline and another 22q11.2 gene, catechol-O-methyltransferase (COMT), on neurotransmission and behavior has been reported. We...

  4. COMT and 5-HT1A-receptor genotypes potentially affect executive functions improvement after cognitive remediation in schizophrenia

    Science.gov (United States)

    Bosia, Marta; Bechi, Margherita; Pirovano, Adele; Buonocore, Mariachiara; Lorenzi, Cristina; Cocchi, Federica; Bramanti, Placido; Smeraldi, Enrico; Cavallaro, Roberto

    2014-01-01

    Cognitive remediation therapy (CRT) has been proved to improve cognitive deficits in schizophrenia and to enhance functional outcomes of classical rehabilitation. However, CRT outcomes are heterogeneous and predictors of response are still unknown. Genetic variability, especially in the dopaminergic system, has been hypothesized to affect CRT. We previously reported that rs4680 of the catechol-O-methyltrasferase (COMT) influences improvements in executive functions in patients treated with CRT, but this result was not confirmed by other studies. Such inconsistent findings may depend, other than on clinical variables, also on other genes involved in cognition. Recent studies proved that serotonin 1A receptor (5-HT1A-R) regulates dopamine in the prefrontal cortex (PFC), and clinical works suggested a 5-HT1A-R role in cognition. We then analysed possible effects of COMT rs4680 and 5-HT1A-R rs6295 on CRT outcomes, taking into account also clinical and demographic factors. Eighty-six clinically stabilized schizophrenia patients treated with three months CRT were assessed with the Wisconsin Card Sorting Test, as a measure of executive functions, at enrolment and after CRT treatment, and underwent COMT and 5-HT1A-R genotyping. We found a significant main effect of COMT genotype and an interaction with 5-HT1A-R on executive function improvement after CRT. The results suggest that these two polymorphisms may have an additive effect on individual capacity to recover from cognitive deficit, probably through their role on PFC dopaminergic transmission modulation, known to be critical for modulating cognitive functions. PMID:25750798

  5. Association of polymorphism of catechol-o-methyltransferase with depression in patients with type 2 diabetes%儿茶酚氧位甲基转移酶基因多态性与糖尿病伴抑郁的相关性研究

    Institute of Scientific and Technical Information of China (English)

    曹音; 刘广军; 成金罗; 杨科春; 袁勇贵

    2012-01-01

    Objective To study the association of polymorphism of catechol-o-methyltransferase with depression in patients with type 2 diabetes. Methods Using a polymerase chain reaction, vall58met polymorphism of COMT was determined in 246 type 2 diabetes and 186 health control subjects. All of patients with type 2 diabetes received HAMD scoring. HAMD rating scale ^ 17 represented depression; and <7, no depressioa Results Allele G and genotype GG frequencies were higher in T2DM both with and without depression group than in control group (all P<0. 05) and A allele and G/A genotype frequencies were lower in T2DM both with and without depression group than in control group. A/A genotype frequency was higher in male than in female in T2DM without depression (P<0. 05). Prevaleuce of T2DM plus depression was lower in male than in female (P<0. 05). Conclusion (l)The polymorphism of COMT gene vall58met associates with type 2 diabetes plus depression. (2) Male patients with type 2 diabetes show less incident depression than female patients with type 2 diabetes.%目的 探讨儿茶酚氧位甲基转移酶(COMT)Val 158 Met多态性与糖尿病伴抑郁的关联研究.方法 用聚合酶链反应及聚丙烯酰胺凝胶电泳方法,检测246例糖尿病患者和186名健康体检者(对照组)的COMT基因Val 158 Met多态性.用汉密尔顿抑郁量表(HAMD)评定所有糖尿病患者,HAMD≥17分者为糖尿病伴抑郁组,HAMD<7分为糖尿病不伴抑郁组.结果 糖尿病伴抑郁组、糖尿病不伴抑郁组的G等位基因和基因型G/G频率均高于对照组,A等位基因和基因型G/A频率低于对照组(P<0.05).糖尿病不伴抑郁组中,男性基因型A/A分布频率显著高于女性.糖尿病伴抑郁组中,男性比率显著低于女性.结论 COMT基因Val 158 Met多态性与糖尿病伴抑郁症可能存在相关性;男性糖尿病患者较女性可能不易伴发抑郁.

  6. Augusto Comte y sus discípulos ortodoxos frente a la cuestión colonial

    Directory of Open Access Journals (Sweden)

    Tonatiuh Useche Sandoval

    2015-05-01

    Full Text Available This article presents the opposition of Auguste Comte and his disciples to the colonization movement which emanated from Occidental Europe in the 19th century. Even if he considers Europe as the central focus of Humanity, Comte states that European contribution to less advanced populations progress does not reside in colonial domination but in the peaceful spreading of a demonstrable doctrine. In the first part, the overall negative appreciation of Comte on modern colonization will be summarized; then his proposals to value the colonizers and to fight the colonialist statements will be mentioned; finally the case of the French conquest in Algeria will be exposed to compare Comte’s position with that of Tocqueville’s and of Enfantin’s. In the second part, a highlight will be made on the moral influence his disciples exercised in England against external colonisation. The significant role played by his Brazilians disciples against internal colonisation and in favour of the indigenous protection will be then underlined. In conclusion, Comte’s positivism constitutes a form of Eurocentric anti-colonialism.

  7. Cloning and Characterization of a Caffeic Acid O-methyltransferase Gene(COMT) from Hevea brasiliensis%一个橡胶树咖啡酸甲基转移酶基因(COMT)的克隆和表达分析

    Institute of Scientific and Technical Information of China (English)

    戚继艳; 方永军; 龙翔宇; 唐朝荣

    2013-01-01

    咖啡酸甲基转移酶(COMT)是木质素合成途径的关键酶,在植物抗逆反应中发挥重要作用.本研究基于本实验室己建立的橡胶树(Hevea brasiliensis)胶乳EST数据库,对组装后序列(Contig)检索并设计引物,利用PCR技术克隆到一个橡胶树COMT基因,命名为HbCOMT(GenBank登录号为GI:443908530).该基因全长1926 bp,由4个外显子和3个内含子组成,编码368个氨基酸,预测蛋白的分子量为40.58kD,等电点为5.46,具有植物O-甲基转移酶的典型特征.系统进化分析显示HbCOMT1蛋白与蓖麻(Ricinus communis)和葡萄(Vitis vinifera)的COMT聚为一组,其他11种植物的COMT则另成一组.基因表达分析显示HbCOMT1在胶乳中的表达量最高,其次是叶片和树皮,花、芽中的表达量较低,种子中几乎不表达.同时,HbCOMT1基因在胶乳中的表达量随割次增加明显上升,显著受伤害诱导,受死皮调控,但对乙烯利应答不明显.本研究首次从橡胶树中克隆了一个COMT基因,了解了其基因结构与表达特性,推测该基因可能参与乳管的胁迫应答和排胶调控,为深入揭示该基因功能提供基础资料.%Caffeic acid O-methyltransferase (COMT) catalyzes the preferential formation of syringyl (S) monolignol subunits,and acts as a key enzyme in lignin synthesis.COMT is implicated in multiple physiological processes in plants,e.g.the functioning of plant vasculature,and defense responses to biotic and abiotic stresses.Up to now,no literature has been available in the cloning and characterization of COMT genes in Hevea brasiliensis (para rubber tree).Previously,we showed that the levels of a COMT protein increased markedly with tapping in the latex of reopened rubber trees.The expressions of this COMT protein correlated well with the patterns of tapping-enhanced latex yields.Here,by searching the assembled latex EST library (20126 high-quality Sanger ESTs,with average length of 575 bp),a contig annotated as COMT was

  8. Polymorphisms of serotonin receptor 2A and 2C genes and COMT in relation to obesity and type 2 diabetes.

    Directory of Open Access Journals (Sweden)

    Sofia I I Kring

    Full Text Available BACKGROUND: Candidate genes of psychological importance include 5HT2A, 5HT2C, and COMT, implicated in the serotonin, noradrenaline and dopamine pathways, which also may be involved in regulation of energy balance. We investigated the associations of single nucleotide polymorphisms (SNPs of these genes with obesity and metabolic traits. METHODOLOGY/PRINCIPAL FINDINGS: In a population of 166 200 young men examined at the draft boards, obese men (n = 726, BMI> or =31.0 kg/m(2 and a randomly selected group (n = 831 were re-examined at two surveys at mean ages 46 and 49 years (S-46, S-49. Anthropometric, physiological and biochemical measures were available. Logistic regression analyses were used to assess age-adjusted odds ratios. No significant associations were observed of 5HT2A rs6311, 5HT2C rs3813929 and COMT rs4680 with obesity, except that COMT rs4680 GG-genotype was associated with fat-BMI (OR = 1.08, CI = 1.01-1.16. The SNPs were associated with a number of physiological variables; most importantly 5HT2C rs3813929 T-allele was associated with glucose (OR = 4.56, CI = 1.13-18.4 and acute insulin response (OR = 0.65, CI = 0.44-0.94 in S-49. COMT rs4680 GG-genotype was associated with glucose (OR = 1.04, CI = 1.00-1.09. Except for an association between 5HT2A rs6311 and total-cholesterol at both surveys, significant in S-46 (OR = 2.66, CI = 1.11-6.40, no significant associations were observed for the other phenotypes. Significant associations were obtained when combined genotype of 5HT2C rs3813929 and COMT rs4680 were examined in relation to BMI (OR = 1.12, CI = 1.03-1.21, fat-BMI (OR = 1.22, CI = 1.08-1.38, waist (OR = 1.13, CI = 1.04-1.22, and cholesterol (OR = 5.60, CI = 0.99-31.4. Analyses of impaired glucose tolerance (IGT and type 2 diabetes (T2D revealed, a 12.3% increased frequency of 5HT2C rs3813929 T-allele and an 11.6% increased frequency of COMT rs4680 GG-genotype in individuals with IGT or T2D (chi(2, p = 0.05 and p = 0

  9. Berekeningsresultaten met het model galvanisch bedrijf

    NARCIS (Netherlands)

    Ros; J.P.M.

    1986-01-01

    Met het model galvanisch bedrijf zijn computerberekeningen uitgevoerd aan 24 modelbedrijven. Daarbij is met name nagegaan, welke kosten moeten worden gemaakt om welk rendement te verkrijgen bij diverse saneringsvarianten. Het blijkt, dat tegen kosten tussen nul en 300 gulden per verwijderde kilo

  10. Clinical significance of MET in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Mikito; Inokuchi; Sho; Otsuki; Yoshitaka; Fujimori; Yuya; Sato; Masatoshi; Nakagawa; Kazuyuki; Kojima

    2015-01-01

    Chemotherapy has become the global standard treatment for patients with metastatic or unresectable gastric cancer(GC),although outcomes remain unfavorable.Many molecular-targeted therapies inhibiting signaling pathways of various tyrosine kinase receptors have been developed,and monoclonal antibodies targeting human epidermal growth factor receptor 2 or vascular endothelial growth factor receptor 2 have become standard therapy for GC.Hepatocyte growth factor and its receptor,c-MET(MET),play key roles in tumor growth through activated signaling pathways from receptor in GC cells.Genomic amplification of MET leads to the aberrant activation found in GC tumors and is related to survival in patients with GC.This review discusses the clinical significance of MET in GC and examines MET as a potential therapeutic target in patients with GC.Preclinical studies in animal models have shown that MET antibodies or smallmolecule MET inhibitors suppress tumor-cell proliferation and tumor progression in MET-amplified GC cells.These drugs are now being evaluated in clinical trials as treatments for metastatic or unresectable GC.

  11. Werken met een inflammatoire darmziekte in Nederland.

    NARCIS (Netherlands)

    Netjes, J.; Borst, J. de; Rijken, M.

    2011-01-01

    Mensen met de ziekte van Crohn of colitis ulcerosa zijn net zo vaak actief op de arbeidsmarkt als andere Nederlanders. Wel werken ze minder vaak fulltime en heeft het merendeel meer of minder last van de ziekte bij hun werk als gevolg van vermoeidheid, stress of spanning. Mensen met een chronische

  12. XML: De eend met de gouden eieren?

    NARCIS (Netherlands)

    Keulen, van Maurice

    2001-01-01

    XML is al een tijdje één van de hypes. Alles moet met XML. Als kritisch informaticus begint het dan bij mij te kriebelen. Hoezo alles moet met XML? Klinkt een beetje als ik heb een hamer en alles ziet er ineens uit als een spijker. Het kan toch niet waar zijn dat men werkelijk iets heeft uitgevonden

  13. Werken met een inflammatoire darmziekte in Nederland.

    NARCIS (Netherlands)

    Netjes, J.; Borst, J. de; Rijken, M.

    2011-01-01

    Mensen met de ziekte van Crohn of colitis ulcerosa zijn net zo vaak actief op de arbeidsmarkt als andere Nederlanders. Wel werken ze minder vaak fulltime en heeft het merendeel meer of minder last van de ziekte bij hun werk als gevolg van vermoeidheid, stress of spanning. Mensen met een chronische

  14. Bespuiten met calcium kan neusrot voorkomen

    NARCIS (Netherlands)

    Zandstra, G.B.; Marcelis, L.F.M.

    2000-01-01

    Oorzaak van neusrot bij paprika is een calciumtekort in de vrucht. Een bespuiting met calcium vlak na de bloei heeft een zeer gunstig effect. In bijgaande tabel gegevens over het effect van spuiten met calcium op het optreden van neusrot bij paprika

  15. Biobrandstof met het gemak van benzine

    NARCIS (Netherlands)

    Klein Lankhorst, R.M.

    2015-01-01

    Onderzoekers in Wageningen werken aan brandstoffen voor voertuigen die hernieuwbaar zijn en tegelijk hetzelfde gemak kennen als benzine en diesel. In het BioSolar Cellsconsortium werken ze met technieken die geïnspireerd zijn op fotosynthese in planten. Van water wordt met zonlicht waterstof gemaakt

  16. Met apps op eigen benen leren staan

    NARCIS (Netherlands)

    Jan-Pieter Teunisse

    2012-01-01

    Mensen met autisme kunnen in de toekomst zelfstandiger wonen, werken en studeren met behulp van `digitale coaches' op hun mobieltje, iPad of iPod. Bij het testen van deze apps en andere nieuwe technologische hulpmiddelen, is ook de HAN betrokken. `ICT-oplossingen kunnen iemand helpen om meer regie

  17. André Comte-Sponville, L’Amour en quatre leçons de philosophie. Amour et Bonheur (DVD 1)

    OpenAIRE

    Goarzin, Maël

    2013-01-01

    Le DVD 1, qui fait partie d’un coffret de quatre leçons de philosophie sur le thème de l’amour, est une conférence d’André Comte-Sponville, proposée par Robert Maggiori dans le cadre des Master class de Libération. En une heure, Comte-Sponville aborde le thème de l’amour et du bonheur. Plus précisément, il questionne la possibilité de ce lien entre amour et bonheur : un amour heureux est-il possible ? Pour répondre à cette question, Comte-Sponville distingue trois sortes d’amour, correspondan...

  18. ZNF804a regulates expression of the schizophrenia-associated genes PRSS16, COMT, PDE4B, and DRD2.

    Directory of Open Access Journals (Sweden)

    Matthew J Girgenti

    Full Text Available ZNF804a was identified by a genome-wide association study (GWAS in which a single nucleotide polymorphism (SNP rs1344706 in ZNF804a reached genome-wide statistical significance for association with a combined diagnosis of schizophrenia (SZ and bipolar disorder. Although the molecular function of ZNF804a is unknown, the amino acid sequence is predicted to contain a C2H2-type zinc-finger domain and suggests ZNF804a plays a role in DNA binding and transcription. Here, we confirm that ZNF804a directly contributes to transcriptional control by regulating the expression of several SZ associated genes and directly interacts with chromatin proximal to the promoter regions of PRSS16 and COMT, the two genes we find upregulated by ZNF804a. Using immunochemistry we establish that ZNF804a is localized to the nucleus of rat neural progenitor cells in culture and in vivo. We demonstrate that expression of ZNF804a results in a significant increase in transcript levels of PRSS16 and COMT, relative to GFP transfected controls, and a statistically significant decrease in transcript levels of PDE4B and DRD2. Furthermore, we show using chromatin immunoprecipitation assays (ChIP that both epitope-tagged and endogenous ZNF804a directly interacts with the promoter regions of PRSS16 and COMT, suggesting a direct upregulation of transcription by ZNF804a on the expression of these genes. These results are the first to confirm that ZNF804a regulates transcription levels of four SZ associated genes, and binds to chromatin proximal to promoters of two SZ genes. These results suggest a model where ZNF804a may modulate a transcriptional network of SZ associated genes.

  19. Hybridization of downregulated-COMT transgenic switchgrass lines with field-selected switchgrass for improved biomass traits

    Energy Technology Data Exchange (ETDEWEB)

    Baxter, Holly L.; Alexander, Lisa W.; Mazarei, Mitra; Haynes, Ellen; Turner, Geoffrey B.; Sykes, Robert W.; Decker, Stephen R.; Davis, Mark F.; Dixon, Richard A.; Wang, Zeng-Yu; Neal Stewart, C.

    2016-01-21

    Transgenic switchgrass (Panicum virgatum L.) has been produced for improved cell walls for biofuels. For instance, downregulated caffeic acid 3-O-methyltransferase (COMT) switchgrass produced significantly more biomass and biofuel than the non-transgenic progenitor line. In the present study we sought to further improve biomass characteristics by crossing the downregulated COMT T1 lines with high-yielding switchgrass accessions in two genetic backgrounds ('Alamo' and 'Kanlow'). Crosses and T2 progeny analyses were made under greenhouse conditions to assess maternal effects, plant morphology and yield, and cell wall traits. Female parent type influenced morphology, but had no effect on cell wall traits. T2 hybrids produced with T1 COMT-downregulated switchgrass as the female parent were taller, produced more tillers, and produced 63% more biomass compared with those produced using the field selected accession as the female parent. Transgene status (presence or absence of transgene) influenced both growth and cell wall traits. T2 transgenic hybrids were 7% shorter 80 days after sowing and produced 43% less biomass than non-transgenic null-segregant hybrids. Cell wall-related differences included lower lignin content, reduced syringyl-to-guaiacyl (S/G) lignin monomer ratio, and a 12% increase in total sugar release in the T2 transgenic hybrids compared to non-transgenic null segregants. This is the first study to evaluate the feasibility of transferring the low-recalcitrance traits associated with a transgenic switchgrass line into high-yielding field varieties in an attempt to improve growth-related traits. Our results provide insights into the possible improvement of switchgrass productivity via biotechnology paired with plant breeding.

  20. Association of copy number polymorphisms at the promoter and translated region of COMT with Japanese patients with schizophrenia.

    Science.gov (United States)

    Higashiyama, Ryoko; Ohnuma, Tohru; Takebayashi, Yuto; Hanzawa, Ryo; Shibata, Nobuto; Yamamori, Hidenaga; Yasuda, Yuka; Kushima, Itaru; Aleksic, Branko; Kondo, Kenji; Ikeda, Masashi; Hashimoto, Ryota; Iwata, Nakao; Ozaki, Norio; Arai, Heii

    2016-04-01

    Chromosome 22q11.2 deletion syndrome and genetic variations including single-nucleotide polymorphism (SNP) and copy number variation (CNV) in catechol-O-methyltransferase (COMT) situated at 22q11.2 remains controversial. Here, the genetic relationship between COMT and Japanese patients with schizophrenia was investigated by examining whether the SNPs correlated with schizophrenia based on a common disease-common variant hypothesis. Additionally, 22q11.2DS were screened based on a common disease-rare variant hypothesis; low-frequency CNVs situated at two COMT promoters and exons were investigated based on the low-frequency variants with an intermediate effect; and positive findings from the first stage were reconfirmed using a second-stage replication study including a larger sample size. Eight SNPs and 10 CNVs were investigated using Taqman SNP and CNV quantitative real-time polymerase chain reaction method. For the first-stage analysis, 513 unrelated Japanese patients with schizophrenia and 705 healthy controls were examined. For the second-stage replication study, positive findings from the first stage were further investigated using a larger sample size, namely 1,854 patients with schizophrenia and 2,137 controls. The first-stage analysis showed significant associations among schizophrenia, intronic SNP rs165774, CNV6 situated at promoter 1, CNV8 at exon 6, and CNV9 at exon 7. The second-stage study showed that intronic SNP rs165774 (χ(2)  = 8.327, P = 0.0039), CNV6 (χ(2)  = 19.66, P = 0.00005), and CNV8 (χ(2)  = 16.57, P = 0.00025) were significantly associated with schizophrenia. Large and rare CNVs as well as low-frequency CNVs and relatively small CNVs, namely schizophrenia.

  1. APOE and COMT polymorphisms are complementary biomarkers of status, stability, and transitions in normal aging and early mild cognitive impairment

    Directory of Open Access Journals (Sweden)

    Roger A Dixon

    2014-09-01

    Full Text Available Objective: Research has reported associations among selected genetic susceptibility biomarkers and risk of (a normal cognitive aging decrements, (b established mild cognitive impairment (MCI, and (c sporadic Alzheimer’s disease (AD. In focusing on the transitional normal-to-early MCI phase, we examine associations among three theoretically relevant polymorphisms (APOE [rs429358, rs7412], BDNF [rs6265], COMT [rs4680] and both baseline cognitive status (MCI versus normal aging and two-wave (four-year longitudinal stability or change profiles. The latter included three profiles: (a stable as normal aging, (b stable or chronic impairment (MCI-to-MCI, and (c emergence of impairment (normal-to-MCI. Method: Genotyped older adults (n = 237 at baseline; age range = 64-91; 62% women from the Victoria Longitudinal Study were examined for (a independent and interactive associations of three genetic polymorphisms with (b two objectively classified cognitive status groups (not-impaired controls (NIC and MCI at (c both baseline and across a two-wave (four-year longitudinal interval. Results: First, logistic regression revealed that the presence of at least one APOE ε4 allele (the risk factor for AD was linked to greater baseline risk of objective MCI. Second, multinomial logistic regression revealed that (a the presence of an APOE ε4 allele was associated with an increased risk of 4-year MCI status stability (chronicity, and (b the COMT homozygous risk genotype (G/G or Val/Val was associated with an increased risk of both MCI-to-MCI stability (chronicity and emerging NIC-to-MCI conversion. Discussion: Both chronicity and emergence of objectively classified early cognitive impairment may be genetically heterogeneous phenomena, with influences from a panel of both normal cognitive aging (COMT and AD-related (APOE polymorphisms.

  2. Analysis of peeling decoder for MET ensembles

    CERN Document Server

    Hinton, Ryan

    2009-01-01

    The peeling decoder introduced by Luby, et al. allows analysis of LDPC decoding for the binary erasure channel (BEC). For irregular ensembles, they analyze the decoder state as a Markov process and present a solution to the differential equations describing the process mean. Multi-edge type (MET) ensembles allow greater precision through specifying graph connectivity. We generalize the the peeling decoder for MET ensembles and derive analogous differential equations. We offer a new change of variables and solution to the node fraction evolutions in the general (MET) case. This result is preparatory to investigating finite-length ensemble behavior.

  3. Mars MetNet Mission Payload Overview

    Science.gov (United States)

    Harri, A.-M.; Haukka, H.; Alexashkin, S.; Guerrero, H.; Schmidt, W.; Genzer, M.; Vazquez, L.

    2012-09-01

    A new kind of planetary exploration mission for Mars is being developed in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission [1] is based on a new semi-hard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide crucial scientific data about the Martian atmospheric phenomena.

  4. Assessment of cellular estrogenic activity based on estrogen receptor-mediated reduction of soluble-form catechol-O-methyltransferase (COMT) expression in an ELISA-based system.

    Science.gov (United States)

    Ho, Philip Wing-Lok; Tse, Zero Ho-Man; Liu, Hui-Fang; Lu, Song; Ho, Jessica Wing-Man; Kung, Michelle Hiu-Wai; Ramsden, David Boyer; Ho, Shu-Leong

    2013-01-01

    Xenoestrogens are either natural or synthetic compounds that mimic the effects of endogenous estrogen. These compounds, such as bisphenol-A (BPA), and phthalates, are commonly found in plastic wares. Exposure to these compounds poses major risk to human health because of the potential to cause endocrine disruption. There is huge demand for a wide range of chemicals to be assessed for such potential for the sake of public health. Classical in vivo assays for endocrine disruption are comprehensive but time-consuming and require sacrifice of experimental animals. Simple preliminary in vitro screening assays can reduce the time and expense involved. We previously demonstrated that catechol-O-methyltransferase (COMT) is transcriptionally regulated by estrogen via estrogen receptor (ER). Therefore, detecting corresponding changes of COMT expression in estrogen-responsive cells may be a useful method to estimate estrogenic effects of various compounds. We developed a novel cell-based ELISA to evaluate cellular response to estrogenicity by reduction of soluble-COMT expression in ER-positive MCF-7 cells exposed to estrogenic compounds. In contrast to various existing methods that only detect bioactivity, this method elucidates direct physiological effect in a living cell in response to a compound. We validated our assay using three well-characterized estrogenic plasticizers - BPA, benzyl butyl phthalate (BBP), and di-n-butyl phthalate (DBP). Cells were exposed to either these plasticizers or 17β-estradiol (E2) in estrogen-depleted medium with or without an ER-antagonist, ICI 182,780, and COMT expression assayed. Exposure to each of these plasticizers (10(-9)-10(-7)M) dose-dependently reduced COMT expression (pvitro assays of similar sensitivity. To satisfy the demand for in vitro assays targeting different cellular components, a cell-based COMT assay provides useful initial screening to supplement the current assessments of xenoestrogens for potential estrogenic activity.

  5. Polymorphisms of serotonin receptor 2A and 2C genes and COMT in relation to obesity and type 2 diabetes

    DEFF Research Database (Denmark)

    Kring, Sofia I I; Werge, Thomas; Holst, Claus

    2009-01-01

    BACKGROUND: Candidate genes of psychological importance include 5HT2A, 5HT2C, and COMT, implicated in the serotonin, noradrenaline and dopamine pathways, which also may be involved in regulation of energy balance. We investigated the associations of single nucleotide polymorphisms (SNPs......) of these genes with obesity and metabolic traits. METHODOLOGY/PRINCIPAL FINDINGS: In a population of 166 200 young men examined at the draft boards, obese men (n = 726, BMI> or =31.0 kg/m(2)) and a randomly selected group (n = 831) were re-examined at two surveys at mean ages 46 and 49 years (S-46, S-49...

  6. Acetylcholinesterase converts Met5-enkephalin-containing peptides to Met5-enkephalin.

    Science.gov (United States)

    Dowton, M; Boelen, M

    1988-11-22

    Acetylcholinesterase (AChE; E.C. 3.1.1.7) was incubated with a number of enkephalin-containing neuropeptides found in the bovine adrenal medulla. Met5-enkephalin and Leu5-enkephalin were the most stable of the peptides studied, while precursors of Met5-enkephalin were converted to Met5-enkephalin. AChE is therefore capable of limited peptidase activity on Met5-enkephalin precursors. The enzyme hydrolysed the Met5-enkephalin precursor BAM-12P on the C-terminal side of the pair of basic amino acid residues, and cleaved basic amino acids from the carboxy-terminal of Met5-enkephalin-Arg6 and Met5-enkephalin-Arg6-Arg7. These results indicate that AChE, acting alone, is capable of the same pattern of enkephalin processing as that observed in the adrenal medulla.

  7. Prof. Zhu Zuoyan Met with ISI Delegation

    Institute of Scientific and Technical Information of China (English)

    Liu Xiuping; Chen Huai

    2007-01-01

    @@ On March 27, Prof. Zhu Zuoyan, Vice President of NSFC, met with a three-member delegation from the Institute for Scientific Information (ISI), USA headed by Dr. James Testa, Director of Editorial Development of ISI.

  8. Palmzaadkever opsporen met lichtval en alcohol

    NARCIS (Netherlands)

    Bloemhard, C.M.J.

    2006-01-01

    De palmzaadkever houdt er een verborgen levenswijze op na. Met een lichtval zijn de volwassenen, vliegende vrouwtjes goed te vangen. Tijdige signalering verbetert de bestrijding, maar vooral schoon uitgangsmateriaal importeren verlaagt de infectiedruk

  9. Ervaringen en perspectieven van zaadcoating met pesticiden

    NARCIS (Netherlands)

    Ester, A.; Huiting, H.; Putter, de H.

    2005-01-01

    Zaadbehandeling is doorgaans een uitgelezen kans om gebruik van gewasbeschermingsmiddelen fors terug te dringen. Coating van het zaad met insecticiden kan in een aantal situaties een effectieve bestrijdingsmethode zijn. Doordat de volvelds-, kweekplaat-, plantvoetbehandeling en soms een gewasbehande

  10. Roestvrij stalen trog met opstap voldoet goed

    NARCIS (Netherlands)

    Hoofs, A.

    1995-01-01

    Uit onderzoek op het Varkensproefbedrijf in Sterksel blijkt dat de roestvrij stalen trog met opstap en schuine voorkant, ondanks het hogere investeringsbedrag, perspectieven biedt voor toepassing in de vleesvarkenshouderij.

  11. Mars MetNet Precursor Mission Status

    Science.gov (United States)

    Harri, A.-M.; Aleksashkin, S.; Guerrero, H.; Schmidt, W.; Genzer, M.; Vazquez, L.; Haukka, H.

    2013-09-01

    We are developing a new kind of planetary exploration mission for Mars in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semi-hard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor [1] mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide significant insights in to the Martian atmospheric behavior. The key technologies of the MetNet Lander have been qualified and the electrical qualification model (EQM) of the payload bay has been built and successfully tested.

  12. Mars MetNet Mission Status

    Science.gov (United States)

    Harri, A.-M.; Aleksashkin, S.; Arruego, I.; Schmidt, W.; Genzer, M.; Vazquez, L.; Haukka, H.; Palin, M.; Nikkanen, T.

    2015-10-01

    New kind of planetary exploration mission for Mars is under development in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semihard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor [1] mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide significant insights in to the Martian atmospheric behavior. The key technologies of the MetNet Lander have been qualified and the electrical qualification model (EQM) of the payload bay has been built and successfully tested.

  13. Afvangen van fosfaat uit bloembollensector met ijzerzand

    NARCIS (Netherlands)

    Chardon, W.J.; Groenenberg, J.E.; Jansen, S.; Buijert, A.; Talens, R.; Krol, A.F.

    2014-01-01

    In het oppervlaktewater van de Bollenstreek is de fosfaatconcentratie veel hoger dan de norm van de Europese Kaderrichtlijn Water. Met ijzerzand, een nevenproduct van drinkwaterproductie, kan fosfaat worden afgevangen. Het hoogheemraadschap van Rijnland heeft drie maatregelen op basis van ijzerzand

  14. Met een Happy Meal duurzaam leren handelen

    NARCIS (Netherlands)

    Noorduyn, L.; Wals, A.E.J.

    2010-01-01

    Afgestudeerden van groene opleidingen moeten over duurzaamheidscompetenties beschikken, willen ze problemen echt op kunnen lossen. Bijvoorbeeld “omgaan met onzekerheid” en “inleven in een ander”. Maar hoe breng je een student die competenties bij?

  15. MMPM - Mars MetNet Precursor Mission

    Science.gov (United States)

    Harri, A.-M.; Schmidt, W.; Pichkhadze, K.; Linkin, V.; Vazquez, L.; Uspensky, M.; Polkko, J.; Genzer, M.; Lipatov, A.; Guerrero, H.; Alexashkin, S.; Haukka, H.; Savijarvi, H.; Kauhanen, J.

    2008-09-01

    We are developing a new kind of planetary exploration mission for Mars - MetNet in situ observation network based on a new semi-hard landing vehicle called the Met-Net Lander (MNL). The eventual scope of the MetNet Mission is to deploy some 20 MNLs on the Martian surface using inflatable descent system structures, which will be supported by observations from the orbit around Mars. Currently we are working on the MetNet Mars Precursor Mission (MMPM) to deploy one MetNet Lander to Mars in the 2009/2011 launch window as a technology and science demonstration mission. The MNL will have a versatile science payload focused on the atmospheric science of Mars. Detailed characterization of the Martian atmospheric circulation patterns, boundary layer phenomena, and climatology cycles, require simultaneous in-situ measurements by a network of observation posts on the Martian surface. The scientific payload of the MetNet Mission encompasses separate instrument packages for the atmospheric entry and descent phase and for the surface operation phase. The MetNet mission concept and key probe technologies have been developed and the critical subsystems have been qualified to meet the Martian environmental and functional conditions. Prototyping of the payload instrumentation with final dimensions was carried out in 2003-2006.This huge development effort has been fulfilled in collaboration between the Finnish Meteorological Institute (FMI), the Russian Lavoschkin Association (LA) and the Russian Space Research Institute (IKI) since August 2001. Currently the INTA (Instituto Nacional de Técnica Aeroespacial) from Spain is also participating in the MetNet payload development. To understand the behavior and dynamics of the Martian atmosphere, a wealth of simultaneous in situ observations are needed on varying types of Martian orography, terrain and altitude spanning all latitudes and longitudes. This will be performed by the Mars MetNet Mission. In addition to the science aspects the

  16. MetNet - Martian Network Mission

    Science.gov (United States)

    Harri, A.-M.

    2009-04-01

    We are developing a new kind of planetary exploration mission for Mars - MetNet in situ observation network based on a new semi-hard landing vehicle called the Met-Net Lander (MNL). The actual practical mission development work started in January 2009 with participation from various countries and space agencies. The scientific rationale and goals as well as key mission solutions will be discussed. The eventual scope of the MetNet Mission is to deploy some 20 MNLs on the Martian surface using inflatable descent system structures, which will be supported by observations from the orbit around Mars. Currently we are working on the MetNet Mars Precursor Mission (MMPM) to deploy one MetNet Lander to Mars in the 2009/2011 launch window as a technology and science demonstration mission. The MNL will have a versatile science payload focused on the atmospheric science of Mars. Detailed characterization of the Martian atmospheric circulation patterns, boundary layer phenomena, and climatology cycles, require simultaneous in-situ measurements by a network of observation posts on the Martian surface. The scientific payload of the MetNet Mission encompasses separate instrument packages for the atmospheric entry and descent phase and for the surface operation phase. The MetNet mission concept and key probe technologies have been developed and the critical subsystems have been qualified to meet the Martian environmental and functional conditions. This development effort has been fulfilled in collaboration between the Finnish Meteorological Institute (FMI), the Russian Lavoschkin Association (LA) and the Russian Space Research Institute (IKI) since August 2001. Currently the INTA (Instituto Nacional de Técnica Aeroespacial) from Spain is also participating in the MetNet payload development.

  17. Polimorfismos dos genes do receptor de serotonina (5-HT2A e da catecol-O-metiltransferase (COMT: fatores desencadeantes da fibromialgia? Serotonin receptor (5-HT 2A and catechol-O-methyltransferase (COMT gene polymorphisms: Triggers of fibromyalgia?

    Directory of Open Access Journals (Sweden)

    Josie Budag Matsuda

    2010-04-01

    Full Text Available INTRODUÇÃO: A fibromialgia é uma síndrome reumática caracterizada por dor difusa e crônica associada a fadiga, insônia, ansiedade, depressão, perda de memória e tontura. Embora os mecanismos fisiológicos que controlam a fibromialgia não tenham sido estabelecidos, fatores neuroendócrinos, genéticos ou moleculares podem estar envolvidos. OBJETIVO: O objetivo do presente estudo foi caracterizar os polimorfismos dos genes do receptor de serotonina (5-HT2A e da catecolO-metiltransferase (COMT em pacientes brasileiros com fibromialgia, a fim de avaliar sua participação na etiologia da doença. MATERIAL E MÉTODOS: O DNA genômico extraído de 102 amostras de sangue (51 pacientes, 51 controles foi usado para a caracterização molecular dos polimorfismos dos genes 5-HT2A e COMT, por meio de PCR-RFLP. RESULTADOS: A análise molecular dos polimorfismos do gene 5-HT2A demonstrou frequências de 25,49% C/C, 49,02% T/C e 25,49% T/T, nos pacientes com fibromialgia, e 17,65% C/C, 62,74% T/C e 19,61% T/T, no grupo controle, não apresentando diferença significativa entre o grupo de pacientes e o grupo controle. Os polimorfismos do gene da COMT em pacientes com fibromialgia apresentaram uma frequência de 17,65% e 45,10% para os genótipos H/H e L/H, respectivamente. No grupo controle, as frequências foram de 29,42%, para H/H, e 60,78%, para L/H, sem diferença significativa entre ambos os grupos. Entretanto, houve diferença significativa na frequência do genótipo L/L em pacientes (37,25% e controles (9,8%, o que permitiu a diferenciação entre os dois grupos. CONCLUSÃO: A frequência do genótipo L/L foi maior nos pacientes com fibromialgia. Apesar de a fibromialgia envolver uma situação poligênica e fatores ambientais, o estudo molecular do SNP rs4680 do gene da COMT pode auxiliar a identificação de indivíduos suscetíveis.INTRODUCTION: Fibromyalgia is a rheumatic syndrome characterized by diffuse and chronic pain associated with

  18. Mars MetNet Mission Status

    Science.gov (United States)

    Harri, Ari-Matti; Aleksashkin, Sergei; Arruego, Ignacio; Schmidt, Walter; Genzer, Maria; Vazquez, Luis; Haukka, Harri

    2015-04-01

    New kind of planetary exploration mission for Mars is under development in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semi-hard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor [1] mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide significant insights in to the Martian atmospheric behavior. The key technologies of the MetNet Lander have been qualified and the electrical qualification model (EQM) of the payload bay has been built and successfully tested. 1. MetNet Lander The MetNet landing vehicles are using an inflatable entry and descent system instead of rigid heat shields and parachutes as earlier semi-hard landing devices have used. This way the ratio of the payload mass to the overall mass is optimized. The landing impact will burrow the payload container into the Martian soil providing a more favorable thermal environment for the electronics and a suitable orientation of the telescopic boom with external sensors and the radio link antenna. It is planned to deploy several tens of MNLs on the Martian surface operating at least partly at the same time to allow meteorological network science. 2. Scientific Payload The payload of the two MNL precursor models includes the following instruments: Atmospheric instruments: 1. MetBaro Pressure device 2. MetHumi Humidity device 3. MetTemp Temperature sensors Optical devices: 1. PanCam Panoramic 2. MetSIS Solar irradiance sensor with OWLS optical wireless system for data transfer 3. DS Dust sensor The descent processes dynamic properties are monitored by a special 3-axis accelerometer combined with a 3-axis gyrometer. The data will be sent via auxiliary beacon antenna throughout the

  19. Mars MetNet Mission Payload Overview

    Science.gov (United States)

    Haukka, H.; Harri, A.-M.; Alexashkin, S.; Guerrero, H.; Schmidt, W.; Genzer, M.; Vazquez, L.

    2012-04-01

    A new kind of planetary exploration mission for Mars is being developed in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semi-hard landing vehicle called MetNet Lander (MNL). The main idea behind the MetNet landing vehicles is to use a state-of-the-art inflatable entry and descent system instead of rigid heat shields and parachutes as earlier semi-hard landing devices have used. This way the ratio of the payload mass to the overall mass is optimized and more mass and volume resources are spared for the science payload. The vehicle decelerates its entry speed using the inflatable structure and final landing sequence includes a cone headed body penetrating the Martian soil. It is planned to deploy several tens of MNLs on the Martian surface operating at least partly at the same time to allow meteorological network science. The payload of the two MNL precursor models includes the following instruments: Atmospheric instruments: - Pressure device (MetBaro): mass 100g, measurement range 0..1015 hPa. - Humidity device (MetHumi): mass 15g, measurement range 0..100%RH. - Temperature sensors (MetTemp): mass 2g each, measurement range -110C..+30C. Optical devices: - Panoramic camera (PanCam): mass 100g, FOV 4 lenses mounted at 90 deg - Solar irradiance sensor (MetSIS) with optical wireless system (OWLS) for data transfer: mass 115g (MetSIS) and 7g (OWLS module), wavelength range 190..1100nm. MetSIS equipped with 28 optical detectors, two temperature sensors and two solar incidence angle detectors. - Dust sensor (DS): mass 42g, resolution: 10 particles / cm3. Composition and structure device: - Magnetometer (MOURA): mass 80g, measurement range: ±30uT. MetNet Mission payload instruments are specially designed to operate in very low power conditions. MNL flexible solar panels provides a total of

  20. [Logic model of the Franche-Comté Regional Health Project: advantages and limitations for the evaluation process].

    Science.gov (United States)

    Michaud, Claude; Sannino, Nadine; Duboudin, Cédric; Baudier, François; Guillin, Caroline; Billondeau, Christine; Mansion, Sylvie

    2014-01-01

    The French "Hospitals, patients, health and territories" law of July 2009 created the Regional Health Project (PRS) to support regional health policy, and requires evaluation of these projects. The construction of these projects, which includes prevention planning, care planning, and medical and social welfare planning, presents an unprecedented complexity in France, where evaluation programmes are still in their infancy. To support future evaluations, the Franche-Comté Regional Health Agency (ARS FC), assisted by the expertise of EFECT Consultants, decided to reconstruct the PRS logic model. This article analyzes the advantages and limitations of this approach. The resulting logic model allows visualization of the strategy adopted to achieve the Franche-Comté PRS ambitions and expected results. The model highlights four main aspects of structural change to the health system, often poorly visible in PRS presentation documents. This model also establishes links with the usual public policy evaluation issues and facilitates their prioritization. This approach also provides a better understanding of the importance of analysis of the programme construction in order to be effective rather than direct analysis of the effects, which constitutes the natural tendency of current practice. The main controversial limit concerns the retrospective design of the PRS framework, both in terms of the reliability of interpretation and adoption by actors not directly involved in this initiative.

  1. Polymorphism in xenobiotic and estrogen metabolizing genes, exposure to perfluorinated compounds and subsequent breast cancer risk: A nested case-control study in the Danish National Birth Cohort.

    Science.gov (United States)

    Ghisari, Mandana; Long, Manhai; Røge, Durita Mohr; Olsen, Jørn; Bonefeld-Jørgensen, Eva C

    2017-04-01

    In the present case-cohort study based on prospective data from Danish women, we aimed to estimate the main effect of polymorphisms in genes known to be involved in the steroid hormone metabolic pathway and xenobiotic metabolism on the risk of developing breast cancer. We also studied a possible effect measure modification between genotypes and levels of serum perfluoroalkylated substances (PFASs) on the risk to breast cancer. We have previously reported a weak association between serum PFASs levels and the risk of breast cancer for this study population of Danish pregnant nulliparous women as well as in a smaller case-control study of Greenlandic women. The study population consisted of 178 breast cancer cases and 233 controls (tabnulliparous and frequency matched on age) nested within the Danish National Birth Cohort (DNBC), which was established in 1996-2002. Blood samples were drawn at the time of enrollment (6-14 week of gestation). Serum levels of 10 perfluorocarboxylated acids (PFCAs), 5 perfluorosulfonated acids (PFSAs) and 1 sulfonamide (perflurooctane-sulfonamide, PFOSA) were measured. Genotyping was conducted for CYP1A1 (Ile462Val; rs1048943), CYP1B1 (Leu432Val; rs1056836), COMT (Val158Met; rs4680), CYP17A1 (A1→ A2; rs743572); CYP19A1 (C→T; rs10046) by the TaqMan allelic discrimination method. In overall, no significant associations were found between the investigated polymorphisms and the risk of breast cancer in this study among Danish women. The previously found association between PFOSA and risk of breast cancer did vary between different genotypes, with significantly increased risk confined to homozygous carriers of the following alleles: COMT (Met), CYP17 (A1) and CYP19 (C).

  2. Playing nice: a multi-methodological study on the effects of social conformity on memory.

    Science.gov (United States)

    Deuker, Lorena; Müller, Anna R; Montag, Christian; Markett, Sebastian; Reuter, Martin; Fell, Juergen; Trautner, Peter; Axmacher, Nikolai

    2013-01-01

    Conformity is an important aspect of social behavior. Two main motives have been identified: people may adapt their behavior to "play nice" despite knowing better (normative conformity) or they may accept the others' opinion as a valid source of information (informative conformity). Neuroimaging studies can help to distinguish between these two possibilities. Here, we present a functional magnetic resonance imaging (fMRI) study on memory conformity in a real group situation. We investigated the effects of group pressure on activity in hippocampus and anterior cingulate cortex (ACC) which likely support informative and normative memory conformity, respectively. Furthermore, we related the single nucleotide polymorphism (SNP) rs4680 [called Catechol-O-methyltransferase (COMT) Val158Met] on the gene coding for COMT to both behavior and fMRI activation. Homozygous Met-allele carriers (Val-) behaved more conformist than carriers of at least one Val-allele (Val+). In the neuroimaging data, we compared trials in which subjects were confronted with a majority of incorrect group responses to trials in which they were confronted with a majority of correct group responses. We found increased hippocampal activity when the majority of the group was correct, possibly indicating retrieval processes. Moreover, we observed enhanced activity in the ACC when the majority of the group was incorrect, suggesting that conformity was mostly normative. Most interestingly, this latter effect was more pronounced for Val- as compared to Val+ participants. This offers a speculative explanation for the higher behavioral levels of social conformity in Val- allele carriers, because their subjectively perceived conflict in the presence of an incorrect group majority may have been higher. Overall, this study demonstrates how the mechanisms leading to complex social behavior such as conformity can be studied by combining genetic analyses and fMRI in social neuroscience paradigms.

  3. Alcoholism: genes and mechanisms.

    Science.gov (United States)

    Oroszi, Gabor; Goldman, David

    2004-12-01

    Alcoholism is a chronic relapsing/remitting disease that is frequently unrecognized and untreated, in part because of the partial efficacy of treatment. Only approximately one-third of patients remain abstinent and one-third have fully relapsed 1 year after withdrawal from alcohol, with treated patients doing substantially better than untreated [1]. The partial effectiveness of strategies for prevention and treatment, and variation in clinical course and side effects, represent a challenge and an opportunity to better understand the neurobiology of addiction. The strong heritability of alcoholism suggests the existence of inherited functional variants of genes that alter the metabolism of alcohol and variants of other genes that alter the neurobiologies of reward, executive cognitive function, anxiety/dysphoria, and neuronal plasticity. Each of these neurobiologies has been identified as a critical domain in the addictions. Functional alleles that alter alcoholism-related intermediate phenotypes include common alcohol dehydrogenase 1B and aldehyde dehydrogenase 2 variants that cause the aversive flushing reaction; catechol-O-methyltransferase (COMT) Val158Met leading to differences in three aspects of neurobiology: executive cognitive function, stress/anxiety response, and opioid function; opioid receptor micro1 (OPRM1) Asn40Asp, which may serve as a gatekeeper molecule in the action of naltrexone, a drug used in alcoholism treatment; and HTTLPR, which alters serotonin transporter function and appears to affect stress response and anxiety/dysphoria, which are factors relevant to initial vulnerability, the process of addiction, and relapse.

  4. Association study between genetic monoaminergic polymorphisms and OCD response to clomipramine treatment

    Directory of Open Access Journals (Sweden)

    K Miguita

    2011-01-01

    Full Text Available In the present paper, we investigated the 5HTTLPR and STin2 polymorphisms in the promoter region of the serotonin transporter gene (SLC6A4, the G861C polymorphism (rs6296 of the serotonin receptor 1D beta (HTR1B, the T102C (rs6113 and C516T (rs6305 polymorphisms of the serotonin receptor gene subtype 2A (HTR2A, the DAT UTR, DAT intron 8 and DAT intron 14 of the dopamine transporter gene (SLC6A3, the Val-158-Met (rs4680 polymorphism of the COMT and the silent mutation G1287A (rs5569 in the norepinephrine transporter gene (SLC6A2. We genotyped 41 obsessive-compulsive disorder (OCD outpatients, classified as good-responders (n=27 and poor-responders (n=14 to treatment with clomipramine according to the Yale Brown Obsessive-Compulsive Scale (YBOCS. Patients who achieved a reduction in symptoms of 40% or more in YBOCS after 14 weeks of treatment were considered good-responders. Genotypes and alleles distribution of the investigated polymorphisms were compared between both groups. We did not find association between the studied polymorphisms and clomipramine response in our sample.

  5. Acute anxiolytic effects of quetiapine during virtual reality exposure--a double-blind placebo-controlled trial in patients with specific phobia.

    Science.gov (United States)

    Diemer, Julia; Domschke, Katharina; Mühlberger, Andreas; Winter, Bernward; Zavorotnyy, Maxim; Notzon, Swantje; Silling, Karen; Arolt, Volker; Zwanzger, Peter

    2013-11-01

    Anxiety disorders are among the most frequent psychiatric disorders. With regard to pharmacological treatment, antidepressants, the calcium modulator pregabalin and benzodiazepines are recommended according to current treatment guidelines. With regard to acute states of anxiety, so far practically only benzodiazepines provide an immediate anxiolytic effect. However, the risk of tolerance and dependency limits the use of this class of medication. Therefore, there is still a need for alternative pharmacologic strategies. Increasing evidence points towards anxiety-reducing properties of atypical antipsychotics, particularly quetiapine. Therefore, we aimed to evaluate the putative acute anxiolytic effects of this compound, choosing the induction of acute anxiety in patients with specific phobia as a model for the evaluation of ad-hoc anxiolytic properties in a proof-of-concept approach. In a randomized, double-blind, placebo-controlled study, 58 patients with arachnophobia were treated with a single dose of quetiapine XR or placebo prior to a virtual reality spider challenge procedure. Treatment effects were monitored using rating scales for acute anxiety as well as measurements of heart rate and skin conductance. Overall, quetiapine showed significant anxiolytic effects compared to placebo. However, effects were not seen on the primary outcome measure (VAS Anxiety), but were limited to somatic anxiety symptoms. Additionally, a significant reduction of skin conductance was observed. Further exploratory analyses hint towards a mediating role of the (COMT) val158met genotype on treatment response. The present results thus suggest a possible suitability of quetiapine in the acute treatment of anxiety, particularly with regard to somatic symptoms.

  6. Genetic variation in AKT1 is linked to dopamine-associated prefrontal cortical structure and function in humans

    Science.gov (United States)

    Tan, Hao-Yang; Nicodemus, Kristin K.; Chen, Qiang; Li, Zhen; Brooke, Jennifer K.; Honea, Robyn; Kolachana, Bhaskar S.; Straub, Richard E.; Meyer-Lindenberg, Andreas; Sei, Yoshitasu; Mattay, Venkata S.; Callicott, Joseph H.; Weinberger, Daniel R.

    2008-01-01

    AKT1-dependent molecular pathways control diverse aspects of cellular development and adaptation, including interactions with neuronal dopaminergic signaling. If AKT1 has an impact on dopaminergic signaling, then genetic variation in AKT1 would be associated with brain phenotypes related to cortical dopaminergic function. Here, we provide evidence that a coding variation in AKT1 that affects protein expression in human B lymphoblasts influenced several brain measures related to dopaminergic function. Cognitive performance linked to frontostriatal circuitry, prefrontal physiology during executive function, and frontostriatal gray-matter volume on MRI were altered in subjects with the AKT1 variation. Moreover, on neuroimaging measures with a main effect of the AKT1 genotype, there was significant epistasis with a functional polymorphism (Val158Met) in catechol-O-methyltransferase [COMT], a gene that indexes cortical synaptic dopamine. This genetic interaction was consistent with the putative role of AKT1 in dopaminergic signaling. Supportive of an earlier tentative association of AKT1 with schizophrenia, we also found that this AKT1 variant was associated with risk for schizophrenia. These data implicate AKT1 in modulating human prefrontal-striatal structure and function and suggest that the mechanism of this effect may be coupled to dopaminergic signaling and relevant to the expression of psychosis. PMID:18497887

  7. Genetic-linked Inattentiveness Protects Individuals from Internet Overuse: A Genetic Study of Internet Overuse Evaluating Hypotheses Based on Addiction, Inattention, Novelty-seeking and Harm-avoidance

    Directory of Open Access Journals (Sweden)

    Cheng Sun

    2016-06-01

    Full Text Available The all-pervasive Internet has created serious problems, such as Internet overuse, which has triggered considerable debate over its relationship with addiction. To further explore its genetic susceptibilities and alternative explanations for Internet overuse, we proposed and evaluated four hypotheses, each based on existing knowledge of the biological bases of addiction, inattention, novelty-seeking, and harm-avoidance. Four genetic loci including DRD4 VNTR, DRD2 Taq1A, COMT Val158Met and 5-HTTLPR length polymorphisms were screened from seventy-three individuals. Our results showed that the DRD4 4R/4R individuals scored significantly higher than the 2R or 7R carriers in Internet Addiction Test (IAT. The 5-HTTLPR short/short males scored significantly higher in IAT than the long variant carriers. Bayesian analysis showed the most compatible hypothesis with the observed genetic results was based on attention (69.8%, whereas hypotheses based harm-avoidance (21.6%, novelty-seeking (7.8% and addiction (0.9% received little support. Our study suggests that carriers of alleles (DRD4 2R and 7R, 5-HTTLPR long associated with inattentiveness are more likely to experience disrupted patterns and reduced durations of Internet use, protecting them from Internet overuse. Furthermore, our study suggests that Internet overuse should be categorized differently from addiction due to the lack of shared genetic contributions.

  8. Association of the Apolipoprotein E 2 Allele with Concurrent Occurrence of Endometrial Hyperplasia and Endometrial Carcinoma

    Directory of Open Access Journals (Sweden)

    Tatiana I. Ivanova

    2015-01-01

    Full Text Available Genes encoding proteins with antioxidant properties may influence susceptibility to endometrial hyperplasia (EH and endometrial carcinoma (ECa. Patients with EH (n = 89, EH concurrent with ECa (n = 76, ECa (n = 186, and healthy controls (n = 1110 were genotyped for five polymorphic variants in the genes involved in metabolism of lipoproteins (APOE Cys112Arg and Arg158Cys, iron (HFE Cys282Tyr and His63Asp, and catecholamines (COMT Val158Met. Patients and controls were matched by ethnicity (all Caucasians, age, body mass index (BMI, and incidence of hypertension and diabetes. The frequency of the APOE E 2 allele (158Cys was higher in patients with EH + ECa than in controls (P = 0.0012, PBonferroni = 0.018, OR = 2.58, 95% CI 1.49–4.45. The APOE E 4 allele (112Arg was more frequently found in patients with EH than in controls and HFE minor allele G (63Asp had a protective effect in the ECa group, though these results appeared to be nonsignificant after correction for multiple comparisons. The results of the study indicate that E 2 allele might be associated with concurrent occurrence of EH and ECa.

  9. Mammographic density and factors determining it from the point of view of high oncological risks

    Directory of Open Access Journals (Sweden)

    D. A. Vasilyev

    2011-01-01

    Full Text Available There is now extensive proof that high percentage of mammographic density (MD is an independent risk factor for breast cance.r Taking this into account, the research data are summarized with regard to relation of MD to anthropometric, as well as hormonal, genetic and genotoxic factors. There is a negative correlation between MD and such risk factors as age, number of deliveries, BMI and waist-hip ratio. Most inves- tigations show a direct connection between MD and prolactin level or insulin-like growth factor in blood, mostly in premenopaus al women. Relations of MD with blood estrogens, testosterone, sex hormone binding globulin prove to be too diverse to be taken in account of. It is pos- sible that the action of hormones, especially estrogens, is mediated through their metabolites catecholestrogens and / or reactive oxygen spe- cies. There is certain evidence that a genetic component plays a role in MD. It refers to COMT Val158Met, IGF-I rs6220 A> G and UGT1A1 in premenopausal women, and to ESR1 (XbaI и PvuII in menopausal cases.Although it is obvious that the risk of breast cancer related to MD is brought about by many factors, there is a necessity for studying addi- tional criteria modifying the process, as well as for searching means for preventing it.

  10. Linking unfounded beliefs to genetic dopamine availability

    Science.gov (United States)

    Schmack, Katharina; Rössler, Hannes; Sekutowicz, Maria; Brandl, Eva J.; Müller, Daniel J.; Petrovic, Predrag; Sterzer, Philipp

    2015-01-01

    Unfounded convictions involving beliefs in the paranormal, grandiosity ideas or suspicious thoughts are endorsed at varying degrees among the general population. Here, we investigated the neurobiopsychological basis of the observed inter-individual variability in the propensity toward unfounded beliefs. One hundred two healthy individuals were genotyped for four polymorphisms in the COMT gene (rs6269, rs4633, rs4818, and rs4680, also known as val158met) that define common functional haplotypes with substantial impact on synaptic dopamine degradation, completed a questionnaire measuring unfounded beliefs, and took part in a behavioral experiment assessing perceptual inference. We found that greater dopamine availability was associated with a stronger propensity toward unfounded beliefs, and that this effect was statistically mediated by an enhanced influence of expectations on perceptual inference. Our results indicate that genetic differences in dopaminergic neurotransmission account for inter-individual differences in perceptual inference linked to the formation and maintenance of unfounded beliefs. Thus, dopamine might be critically involved in the processes underlying one's interpretation of the relationship between the self and the world. PMID:26483654

  11. Brain imaging, genetics and emotion.

    Science.gov (United States)

    Aleman, André; Swart, Marte; van Rijn, Sophie

    2008-09-01

    This paper reviews the published evidence on genetically driven variation in neurotransmitter function and brain circuits involved in emotion. Several studies point to a role of the serotonin transporter promoter polymorphism in amygdala activation during emotion perception. We also discuss other polymorphisms (e.g. the COMT val158met polymorphism, tryptophan hydroxylase-2 -703 G/T) and putative effects on affective processing in cortical and limbic regions. A different line of research concerns studies with genetic disorders. Although at a less fine-grained level, studies with individuals with aneuploidies of the X chromosome (Turner syndrome and Klinefelter syndrome), who display impairments in emotion processing, have resulted in new insights and hypotheses with regard to X chromosomal influences on brain systems supporting cognition and emotion. These have also implicated a key role for the amygdala. Integration of the emerging evidence, suggests that the study of polymorphisms using brain imaging can potentially elucidate biological pathways and mechanisms contributing to individual differences in brain circuits that may bias behavior and affect risk for psychiatric illness.

  12. Linking unfounded beliefs to genetic dopamine availability

    Directory of Open Access Journals (Sweden)

    Katharina eSchmack

    2015-09-01

    Full Text Available Unfounded convictions involving beliefs in the paranormal, grandiosity ideas or suspicious thoughts are endorsed at varying degrees among the general population. Here, we investigated the neurobiopsychological basis of the observed inter-individual variability in the propensity towards unfounded beliefs. 109 healthy individuals were genotyped for four polymorphisms in the COMT gene (rs6269, rs4633, rs4818 and rs4680, also known as val158met that define common functional haplotypes with substantial impact on synaptic dopamine degradation, completed a questionnaire measuring unfounded beliefs, and took part in a behavioural experiment assessing perceptual inference. We found that greater dopamine availability was associated with a stronger propensity towards unfounded beliefs, and that this effect was mediated by an enhanced influence of expectations on perceptual inference. Our results indicate that genetic differences in dopaminergic neurotransmission account for inter-individual differences in perceptual inference linked to the formation and maintenance of unfounded beliefs. Thus, dopamine might be critically involved in the processes underlying one's interpretation of the relationship between the self and the world.

  13. Genotype status of the dopamine-related catechol-O-methyltransferase (COMT) gene corresponds with desirability of “unhealthy” foods

    NARCIS (Netherlands)

    Wallace, D.L.; Aarts, E.; d'Oleire Uquillas, F.; Dang, L.C.; Greer, S.M.; Jagust, W.J.; D'Esposito, M.

    2015-01-01

    The role of dopamine is extensively documented in weight regulation and food intake in both animal models and humans. Yet the role of dopamine has not been well studied in individual differences for food desirability. Genotype status of the dopamine-related catechol-O-methyltransferase (COMT) gene h

  14. Lack of influence of COMT and NET genes variants on executive functions in schizophrenic and bipolar patients, their first-degree relatives and controls.

    Science.gov (United States)

    Szöke, A; Schürhoff, F; Méary, A; Mathieu, F; Chevalier, F; Trandafir, A; Alter, C; Roy, I; Bellivier, F; Leboyer, M

    2006-07-05

    Abnormal dopaminergic function in the prefrontal cortex (PFC) may be a key factor in the etiopathogeny of schizophrenia and bipolar disorder. Both schizophrenic and bipolar subjects have executive functions (EF) deficits, thought to reflect abnormal PFC function. The main inactivation pathways for dopamine in the PFC are enzymatic cleavage by the Carboxy-O-Methyl-Transferase (COMT) and reuptake by the nor-epinephrine transporter (NET). Our aim in this study was to replicate previous studies that investigated influence of the COMT genotype on EF in schizophrenic subjects, their relatives and controls and extend their scope by including bipolar patients, and their relatives and by exploring NET gene polymorphisms influence on executive performances. We investigated one functional polymorphism of the COMT gene and two polymorphisms of the NET gene. EF were assessed by means of the Trail Making Test (TMT) and the Wisconsin Card Sorting Test (WCST). We assessed the effect of each of the three genotypes on EF for the whole sample (N = 318) and separately in schizophrenic (N = 66), bipolar (N = 94) and healthy subjects (i.e., relatives and controls N = 158). Separate analyses were performed because of the presence, in patients samples, of potentially confounding factors, especially medication. Genotype had no significant effect on the cognitive measures in any of the analyses (for the two EF measures, the three polymorphisms, and the four groups). In our sample we found no evidence in favor of a major effect of COMT or NET polymorphisms on the two tests of EF.

  15. Adipose tissue PCB levels and CYP1B1 and COMT genotypes in relation to breast cancer risk in postmenopausal Danish women

    DEFF Research Database (Denmark)

    Bräuner, Elvira V; Loft, Steffen; Wellejus, Anja;

    2014-01-01

    Exposure to PCBs may be an etiologic factor for breast cancer. The cytochrome P450 1B1 (CYP1B1) and catechol-O-methyltransferase (COMT) enzymes are involved in estrogen metabolism and PCB metabolism, both of which may relate to breast cancer susceptibility. Polymorphisms in genes regulating...

  16. Investigating the genetic basis of theory of mind (ToM: the role of catechol-O-methyltransferase (COMT gene polymorphisms.

    Directory of Open Access Journals (Sweden)

    Haiwei Xia

    Full Text Available The ability to deduce other persons' mental states and emotions which has been termed 'theory of mind (ToM' is highly heritable. First molecular genetic studies focused on some dopamine-related genes, while the genetic basis underlying different components of ToM (affective ToM and cognitive ToM remain unknown. The current study tested 7 candidate polymorphisms (rs4680, rs4633, rs2020917, rs2239393, rs737865, rs174699 and rs59938883 on the catechol-O-methyltransferase (COMT gene. We investigated how these polymorphisms relate to different components of ToM. 101 adults participated in our study; all were genetically unrelated, non-clinical and healthy Chinese subjects. Different ToM tasks were applied to detect their theory of mind ability. The results showed that the COMT gene rs2020917 and rs737865 SNPs were associated with cognitive ToM performance, while the COMT gene rs5993883 SNP was related to affective ToM, in which a significant gender-genotype interaction was found (p = 0.039. Our results highlighted the contribution of DA-related COMT gene on ToM performance. Moreover, we found out that the different SNP at the same gene relates to the discriminative aspect of ToM. Our research provides some preliminary evidence to the genetic basis of theory of mind which still awaits further studies.

  17. Investigating the genetic basis of theory of mind (ToM): the role of catechol-O-methyltransferase (COMT) gene polymorphisms.

    Science.gov (United States)

    Xia, Haiwei; Wu, Nan; Su, Yanjie

    2012-01-01

    The ability to deduce other persons' mental states and emotions which has been termed 'theory of mind (ToM)' is highly heritable. First molecular genetic studies focused on some dopamine-related genes, while the genetic basis underlying different components of ToM (affective ToM and cognitive ToM) remain unknown. The current study tested 7 candidate polymorphisms (rs4680, rs4633, rs2020917, rs2239393, rs737865, rs174699 and rs59938883) on the catechol-O-methyltransferase (COMT) gene. We investigated how these polymorphisms relate to different components of ToM. 101 adults participated in our study; all were genetically unrelated, non-clinical and healthy Chinese subjects. Different ToM tasks were applied to detect their theory of mind ability. The results showed that the COMT gene rs2020917 and rs737865 SNPs were associated with cognitive ToM performance, while the COMT gene rs5993883 SNP was related to affective ToM, in which a significant gender-genotype interaction was found (p = 0.039). Our results highlighted the contribution of DA-related COMT gene on ToM performance. Moreover, we found out that the different SNP at the same gene relates to the discriminative aspect of ToM. Our research provides some preliminary evidence to the genetic basis of theory of mind which still awaits further studies.

  18. Assessment of cellular estrogenic activity based on estrogen receptor-mediated reduction of soluble-form catechol-O-methyltransferase (COMT expression in an ELISA-based system.

    Directory of Open Access Journals (Sweden)

    Philip Wing-Lok Ho

    Full Text Available Xenoestrogens are either natural or synthetic compounds that mimic the effects of endogenous estrogen. These compounds, such as bisphenol-A (BPA, and phthalates, are commonly found in plastic wares. Exposure to these compounds poses major risk to human health because of the potential to cause endocrine disruption. There is huge demand for a wide range of chemicals to be assessed for such potential for the sake of public health. Classical in vivo assays for endocrine disruption are comprehensive but time-consuming and require sacrifice of experimental animals. Simple preliminary in vitro screening assays can reduce the time and expense involved. We previously demonstrated that catechol-O-methyltransferase (COMT is transcriptionally regulated by estrogen via estrogen receptor (ER. Therefore, detecting corresponding changes of COMT expression in estrogen-responsive cells may be a useful method to estimate estrogenic effects of various compounds. We developed a novel cell-based ELISA to evaluate cellular response to estrogenicity by reduction of soluble-COMT expression in ER-positive MCF-7 cells exposed to estrogenic compounds. In contrast to various existing methods that only detect bioactivity, this method elucidates direct physiological effect in a living cell in response to a compound. We validated our assay using three well-characterized estrogenic plasticizers - BPA, benzyl butyl phthalate (BBP, and di-n-butyl phthalate (DBP. Cells were exposed to either these plasticizers or 17β-estradiol (E2 in estrogen-depleted medium with or without an ER-antagonist, ICI 182,780, and COMT expression assayed. Exposure to each of these plasticizers (10(-9-10(-7M dose-dependently reduced COMT expression (p<0.05, which was blocked by ICI 182,780. Reduction of COMT expression was readily detectable in cells exposed to picomolar level of E2, comparable to other in vitro assays of similar sensitivity. To satisfy the demand for in vitro assays targeting different

  19. Inhibition of human catechol-O-methyltransferase (COMT)-mediated O-methylation of catechol estrogens by major polyphenolic components present in coffee.

    Science.gov (United States)

    Zhu, Bao Ting; Wang, Pan; Nagai, Mime; Wen, Yujing; Bai, Hyoung-Woo

    2009-01-01

    In the present study, we investigated the inhibitory effect of three catechol-containing coffee polyphenols, chlorogenic acid, caffeic acid and caffeic acid phenethyl ester (CAPE), on the O-methylation of 2- and 4-hydroxyestradiol (2-OH-E(2) and 4-OH-E(2), respectively) catalyzed by the cytosolic catechol-O-methyltransferase (COMT) isolated from human liver and placenta. When human liver COMT was used as the enzyme, chlorogenic acid and caffeic acid each inhibited the O-methylation of 2-OH-E(2) in a concentration-dependent manner, with IC(50) values of 1.3-1.4 and 6.3-12.5 microM, respectively, and they also inhibited the O-methylation of 4-OH-E(2), with IC(50) values of 0.7-0.8 and 1.3-3.1 microM, respectively. Similar inhibition pattern was seen with human placental COMT preparation. CAPE had a comparable effect as caffeic acid for inhibiting the O-methylation of 2-OH-E(2), but it exerted a weaker inhibition of the O-methylation of 4-OH-E(2). Enzyme kinetic analyses showed that chlorogenic acid and caffeic acid inhibited the human liver and placental COMT-mediated O-methylation of catechol estrogens with a mixed mechanism of inhibition (competitive plus noncompetitive). Computational molecular modeling analysis showed that chlorogenic acid and caffeic acid can bind to human soluble COMT at the active site in a similar manner as the catechol estrogen substrates. Moreover, the binding energy values of these two coffee polyphenols are lower than that of catechol estrogens, which means that coffee polyphenols have higher binding affinity for the enzyme than the natural substrates. This computational finding agreed perfectly with our biochemical data.

  20. Pathways to age of onset of heroin use: a structural model approach exploring the relationship of the COMT gene, impulsivity and childhood trauma.

    Directory of Open Access Journals (Sweden)

    Ting Li

    Full Text Available BACKGROUND: The interaction of the association of dopamine genes, impulsivity and childhood trauma with substance abuse remains unclear. OBJECTIVES: To clarify the impacts and the interactions of the Catechol -O-methyltransferase (COMT gene, impulsivity and childhood trauma on the age of onset of heroin use among heroin dependent patients in China. METHODS: 202 male and 248 female inpatients who meet DSM-IV criteria of heroin dependence were enrolled. Impulsivity and childhood trauma were measured using BIS-11 (Barratt Impulsiveness Scale-11 and ETISR-SF (Early Trauma Inventory Self Report-Short Form. The single nucleotide polymorphism (SNP rs737866 on the COMT gene-which has previously been associated with heroin abuse, was genotyped using a DNA sequence detection system. Structural equations model was used to assess the interaction paths between these factors and the age of onset of heroin use. PRINCIPAL FINDINGS: Chi-square test indicated the individuals with TT allele have earlier age of onset of heroin use than those with CT or CC allele. In the correlation analysis, the severity of childhood trauma was positively correlated to impulsive score, but both of them were negatively related to the age of onset of heroin use. In structure equation model, both the COMT gene and childhood trauma had impacts on the age of onset of heroin use directly or via impulsive personality. CONCLUSIONS: Our findings indicated that the COMT gene, impulsive personality traits and childhood trauma experience were interacted to impact the age of onset of heroin use, which play a critical role in the development of heroin dependence. The impact of environmental factor was greater than the COMT gene in the development of heroin dependence.

  1. Chronisch zieken bij de bedrijfsarts: ervaringen met en oordeel over samenwerking met de huisarts.

    NARCIS (Netherlands)

    Baanders, A.N.

    2004-01-01

    Dit artikel beschrijft de ervaringen met en het oordeel over arbocuratieve samenwerking (ACS) vanuit het perspectief van mensen met somatische chronische aandoeningen. Dit geeft een indruk van de mogelijkheden die ACS volgens chronisch zieken kan hebben bij het terugdringen van ziekteverzuimen en

  2. Relationship between polymorphism of COMT gene and clinical outcomes of depression in patients with type 2 diabetes treated with paroxetine%儿茶酚氧位甲基转移酶基因功能多态性对帕罗西汀治疗2型糖尿病伴抑郁患者疗效的相关性

    Institute of Scientific and Technical Information of China (English)

    刘广军; 成金罗; 曹音

    2012-01-01

    目的:探讨儿茶酚氧位甲基转移酶(COMT)基因功能多态性对帕罗西汀治疗2型糖尿病合并抑郁焦虑患者的疗效的影响.方法:对52例血糖控制不理想的2型糖尿病合并抑郁焦虑患者,治疗前抽取外周静脉血,提取DNA,用PCI技术检测研究对象的基因型,分成Val/Val、Val/Met和Met/Met 3组,在常规降糖治疗基础上加用帕罗西汀每晨一次,每次20 mg,疗程4周,观察治疗前、后汉密尔顿抑郁量表(HAMD)、汉密顿焦虑量表(HAMA)分数、餐后2h血糖(2hPBG)、空腹血糖(FBG)、糖化血红蛋白(HbA1c)、帕罗西汀血药浓度的改变.结果:治疗后不同基因组患者抑郁情绪有改善,HAMD、HAMA、2hPBG、FBG、HbA1c、血药浓度与治疗前比较均有显著性差异(P<0.01),但4周后3基因组间差异并无显著性(P>0.05).结论:对2型糖尿病合并抑郁焦虑患者,加用帕罗西汀治疗能有效改善抑郁症状及更好地控制血糖,COMT基因功能多态性与帕罗西汀疗效差异可能并不相关.%OBJECTIVE To investigate the relationship between the polymorphism of COMT gene and clinical outcomes of depression in patients with type 2 diabetes treated with paroxetine. METHODS Fifty-two type 2 diabetes mellitus patients accompanied with depression were treated with paroxetine(20 mg, qd) for 4 weeks. DNAs of peripheral blood leukocytes from 52 patients with type 2 diabetes were obtained before therapy and were analyzed for genotypes by PCR-RFLP method. They were divided into three groups of Val/Val, Val/Met and Met/Met. Hamilton depression scale(HAMD), Hamilton anxiety scale (HAMA). 2hPGB, FBG, HbAlc levels and plasma concentration were obtained to monitor glycemic control. RESULTS Paroxetine significantly improved the symptoms of depression and anxiety in type 2 diabetes mellitus with depression. At the end of the 4th week, the levels of 2hPBG, FBG, HbAlc and scores of both the HAMD and HANA decreased compared with pre-treat-ment (P<0. 01). But

  3. Portale hypertensie : een experimenteel model met dimethylnitrosamine

    NARCIS (Netherlands)

    O.T. Terpstra (Onno)

    1979-01-01

    textabstractDe behandeling van patiënten met een bloeding uit slokdarmvarices ten gevolge van portale hypertensie levert nog steeds geen bevredigende resultaten op (Sherlock 1978). Operaties die de druk in de vena portae verlagen, zoals een portocavale shunt, zijn effectief wanneer het er om gaat ee

  4. Paprika nog moeilijk te sturen met groeilicht

    NARCIS (Netherlands)

    Hogendonk, L.

    2005-01-01

    De resultaten van een op een paprikabedrijf uitgevoerde proef met drie belichtingssystemen van 5 duizend lux zijn in de afgelopen maanden omgezet in een aantal conclusies. Eén uitkomst was dat de effecten van vaste en bewegende belichting elkaar niet veel ontlopen. Een andere conclusie die kon

  5. Met uitloop meer kans op parasitaire infecties

    NARCIS (Netherlands)

    Eijck, I.A.J.M.

    2003-01-01

    Parasitaire infecties vormen een belangrijk probleem in de biologische- en scharrelhouderij. In een veldinventarisatie van het Praktijkonderzoek van ASG werden meer Ascaris suum (spoelwormen), coccidiën en Toxoplasma gondii gevonden op bedrijven met uitloop dan op bedrijven zonder uitloop. Nader ond

  6. A brief report on mets system

    Digital Repository Service at National Institute of Oceanography (India)

    Fernandes, W.A.

    Mets system is basically a gas monitoring system, used for the detection of underwater gas. The system consists of a sensor, datalogger and energy module. The sensor works on the diffusion techniques. The system can be deployed to a water depth...

  7. Inkoper Innoveer! : Kansen grijpen met innoveren

    NARCIS (Netherlands)

    Reijniers, J.J.A.M.; Gaspersz, J.B.R.; Marijnen, Y.; Roddeman, J.

    2009-01-01

    Dit boek biedt inkopers nieuwe perspectieven, praktische adviezen en kansrijke ideeën om succesvoller te zijn en bij te dragen aan de vernieuwingskracht van hun organisatie. Daarnaast bieden de auteurs een visie waarmee de kansen met inkoop volop zijn te benutten: innovatietalent van leveranciers, s

  8. Allergische consument is tevreden met Santana

    NARCIS (Netherlands)

    Maas, van der M.P.; Schenk, M.F.

    2008-01-01

    Nederland had twee jaar geleden de primeur: Santana, een hyperallergeen appelras voor mensen met appelallergie. Wageningen UR heeft de ervaringen van de consumenten over 2006 en 2007 onderzocht. De vermindering van de allergische reactie is ongeveer volgens verwachting en de tevredenheid blijkt hoog

  9. Met gezonde bijen naar de heide

    NARCIS (Netherlands)

    Cornelissen, B.; Calis, J.

    2010-01-01

    Op 22 maart 2010 kwam een bont gezelschap van bijenhouders van ABTB, ANI en NBV bijeen in Hoenderloo. Het onderwerp die avond was de vraag: “Hoe combineer ik varroabestrijding met de heidedracht?” Hieronder het antwoord en wel in de vorm van de basisprincipes van varroa bestrijding plus een concrete

  10. Consistentie met MS-DOS software

    NARCIS (Netherlands)

    Olsthoorn TN

    1988-01-01

    Zonder de keuze van een zekere standaard-lijn ten aanzien van de software die men zelf gebruikt, kan nauwelijks efficient met een computer worden gewerkt. Onder UNIX en op de Macintosh is het gebruik van programma's en de uitwisseling van gegevens daartussen gestandaardiseerd. Onder MS-DOS

  11. Behandeling non-vitale pulpa met formocresol

    NARCIS (Netherlands)

    Wijk, Pieter Harm

    1971-01-01

    Het principe van de endodontische behandeling volgens de richtlijnen van De Boer is gebaseerd op de gedachte dat het niet nodig is het gehele wortelkanaal te reinigen, mits men er voor zorgt dat de achtergelaten noxen met behulp van een chemischestof - in dit geval formaldehyde - onschadelijk worden

  12. OH-induced oxidation of cyclo-Met-Met. A search for a complexed OH-radical

    DEFF Research Database (Denmark)

    Holcman, J.; Bobrowski, K.; Schöneich, C.;

    1991-01-01

    In the OH radical-induced oxidation of cyclo-Met-Met an OH adduct, cyclo-Met-Met(S therefore OH), absorbing at lambda-max = 390 nm with epsilon-390 cyclo-Met-Met(S therefore OH) = 4500 dm3 mol-1 cm-1 is formed. This adduct reversibly eliminates hydroxide ion, pK(b) = 5.4 +/- 0.1, forming correspo...

  13. La posteridad sociológica de Auguste Comte: Lo normal y lo patológico en Durkheim

    OpenAIRE

    MICHEL BOURDEAU

    2008-01-01

    Este artículo completa un texto que, bajo el título «Ciencia, religión y sociedad en Auguste Comte», fue publicado en el año 2003 en las páginas de esta revista. Después de un breve repaso de los conceptos sociológicos fundamentales del Cours de philosophie positive, se muestra como el pensamiento de Durkheim se constituyó a través de una discusión crítica con el positivismo. Concretamente, se examinan dos momentos fundamentales de dicha confrontación. En primer lugar, se analiza como la dist...

  14. Paranormal experience and the COMT dopaminergic gene: a preliminary attempt to associate phenotype with genotype using an underlying brain theory.

    Science.gov (United States)

    Raz, Amir; Hines, Terence; Fossella, John; Castro, Daniella

    2008-01-01

    Paranormal belief and suggestibility seem related. Given our recent findings outlining a putative association between suggestibility and a specific dopaminergic genetic polymorphism, we hypothesized that similar exploratory genetic data may offer supplementary insights into a similar correlation with paranormal belief. With more affordable costs and better technology in the aftermath of the human genome project, genotyping is increasingly ubiquitous. Compelling brain theories guide specific research hypotheses as scientists begin to unravel tentative relationships between phenotype and genotype. In line with a dopaminergic brain theory, we tried to correlate a specific phenotype concerning paranormal belief with a dopaminergic gene (COMT) known for its involvement in prefrontal executive cognition and for a polymorphism that is positively correlated with suggestibility. Although our preliminary findings are inconclusive, the research approach we outline should pave the road to a more scientific account of elucidating paranormal belief.

  15. Estradiol replacement enhances fear memory formation, impairs extinction and reduces COMT expression levels in the hippocampus of ovariectomized female mice.

    Science.gov (United States)

    McDermott, Carmel M; Liu, Dan; Ade, Catherine; Schrader, Laura A

    2015-02-01

    Females experience depression, posttraumatic stress disorder (PTSD), and anxiety disorders at approximately twice the rate of males, but the mechanisms underlying this difference remain undefined. The effect of sex hormones on neural substrates presents a possible mechanism. We investigated the effect of ovariectomy at two ages, before puberty and in adulthood, and 17β-estradiol (E2) replacement administered chronically in drinking water on anxiety level, fear memory formation, and extinction. Based on previous studies, we hypothesized that estradiol replacement would impair fear memory formation and enhance extinction rate. Females, age 4 weeks and 10 weeks, were divided randomly into 4 groups; sham surgery, OVX, OVX+low E2 (200nM), and OVX+high E2 (1000nM). Chronic treatment with high levels of E2 significantly increased anxiety levels measured in the elevated plus maze. In both age groups, high levels of E2 significantly increased contextual fear memory but had no effect on cued fear memory. In addition, high E2 decreased the rate of extinction in both ages. Finally, catechol-O-methyltransferase (COMT) is important for regulation of catecholamine levels, which play a role in fear memory formation and extinction. COMT expression in the hippocampus was significantly reduced by high E2 replacement, implying increased catecholamine levels in the hippocampus of high E2 mice. These results suggest that estradiol enhanced fear memory formation, and inhibited fear memory extinction, possibly stabilizing the fear memory in female mice. This study has implications for a neurobiological mechanism for PTSD and anxiety disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. MET and Small-Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gelsomino, Francesco, E-mail: francesco.gelsomino@istitutotumori.mi.it [Medical Oncology Unit 1, Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Tumori, Via G. Venezian 1, 20133 Milano (Italy); Rossi, Giulio [Operative Unit of Pathology, Azienda Ospedaliero-Universitaria Policlinico, Via del Pozzo 71, 41124 Modena (Italy); Tiseo, Marcello [Medical Oncology Unit, Azienda Ospedaliero-Universitaria, Viale A. Gramsci 14, 43126 Parma (Italy)

    2014-10-13

    Small-cell lung cancer (SCLC) is one of the most aggressive lung tumors. The majority of patients with SCLC are diagnosed at an advanced stage. This tumor type is highly sensitive to chemo-radiation treatment, with very high response rates, but invariably relapses. At this time, treatment options are still limited and the prognosis of these patients is poor. A better knowledge of the molecular biology of SCLC allowed us to identify potential druggable targets. Among these, the MET/HGF axis seems to be one of the most aberrant signaling pathways involved in SCLC invasiveness and progression. In this review, we describe briefly all recent literature on the different molecular profiling in SCLC; in particular, we discuss the specific alterations involving c-MET gene and their implications as a potential target in SCLC.

  17. MET and Small-Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Francesco Gelsomino

    2014-10-01

    Full Text Available Small-cell lung cancer (SCLC is one of the most aggressive lung tumors. The majority of patients with SCLC are diagnosed at an advanced stage. This tumor type is highly sensitive to chemo-radiation treatment, with very high response rates, but invariably relapses. At this time, treatment options are still limited and the prognosis of these patients is poor. A better knowledge of the molecular biology of SCLC allowed us to identify potential druggable targets. Among these, the MET/HGF axis seems to be one of the most aberrant signaling pathways involved in SCLC invasiveness and progression. In this review, we describe briefly all recent literature on the different molecular profiling in SCLC; in particular, we discuss the specific alterations involving c-MET gene and their implications as a potential target in SCLC.

  18. Angular MET sensor for precise azimuth determination

    Science.gov (United States)

    Zaitsev, Dmitry; Antonov, Alexander; Krishtop, Vladimir

    2016-12-01

    This paper describes using a MET-based low-noise angular motion sensor to precisely determine azimuth direction in a dynamic-scheme method of measuring Earth's rotation velocity vector. The scheme includes installing a sensor on a rotating platform so that it could scan a space and seek for the position of highest Earth's rotation vector projection on its axis. This method is very efficient provided a low-noise sensor is used. We take a low-cost angular sensor based on MET (molecular electronic transduction) technology. Sensors of this kind were originally developed for the seismic activity monitoring and are well-known for very good noise performance and high sensitivity. This approach, combined with use of special signal processing algorithms, allowed for reaching the accuracy of 0.07° for a measurement time of 200 seconds.

  19. Synthesis of [{sup 18}F]Ro41-0960, a potent COMT inhibitor, for use in vivo mapping with PET

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Y.S.; Sugano, Y.; Gatley, S.J. [Brookhaven National Laboratory, Upton, NY (United States)] [and others

    1995-05-01

    Catechol-O-methyltransferase (COMPT; EC 2.1.1.6) is one of the two major enzymes which metabolize the catecholamine neurotransmitters. It is distributed throughout the body and brain and is elevated in breast cancer tissue when it plays a role in estrogen metabolism. It is also an important molecular target in the development of drugs to treat Parkinson`s disease (PD). Because COMT regulates the concentration of important neurotransmitter amines such as dopamine, there is speculation that abnormalities in its activity may be associated with neurological, and psychiatric disorders. Ro41-9060(3,4-dihydroxy-5-nitro-2{prime}-fluorobenzophenone) is a potent, fluorine containing COMT inhibitor which has been reported to cross the blood brain barrier. It is structurally similar to Ro40-7592 which is currently undergoing clinical trials in PD. We report the synthesis of [{sup 18}F]Ro41-0960, for investigation for mapping COMT and for studies of COMT drugs. [{sup 18}F]Ro41-0960 was synthesized by the nucleophilic aromatic substitution reaction with NCA [{sup 18}F] fluoride on a protected precursor (prepared via a five-step synthesis) followed by hydrolysis with HBr (synthesis time of 100 min; radiochemical yield of 5-7% (EOB)). Though Ro41-0960 has been reported to cross the blood brain barrier, PET studies in baboon demonstrated that an almost complete absence of the drug from the brain both at tracer doses and with the addition of unlabeled drug (1.5 mg/kg) at all times through a 90 min experimental interval. The plasma to brain ratios of F-18 average about 40:1. However, high uptake was observed in the kidneys and in other organs which are known to have high COMT. Studies in mice showed that at 30 min after injection of tracer, F-18 in kidneys was largely as [{sup 18}F]Ro-41-0960 and that it could be displaced with unlabeled Ro41-0960. These studies provide the first example of a positron emitter labeled COMT radiotracer.

  20. nMET, A New Target in Recurrent Cancer.

    Science.gov (United States)

    Xie, Yingqiu; Istayeva, Sholpan; Chen, Zhanlin; Tokay, Tursonjan; Zhumadilov, Zhaxybay; Wu, Denglong; Hortelano, Gonzalo; Zhang, Jinfu

    2016-01-01

    Membranous Met is classically identified with its role in cancer metastases, while nuclear Met is associated with a more invasive, aggressive and proliferative form of cancer. Full-length Met or N-terminal transmembrane domain cleaved Met can translocate into nucleus in a cell growth and pH dependent but both ligand-dependent (full length Met) and -independent (cleaved Met) manner. nMET may play greater essential roles in cancer recurrence than membranous Met. For example, in prostate cancer, it has been found that androgen receptor (AR) may inhibit the expression of membranous Met so anti-androgen based prostate cancer therapy may promote the expression of nuclear Met (nMET). We recently found a novel nMET/SOX9/ β-Catenin/AR pathway in relapsed prostate cancer which may contribute to the formation of the feedback loop of AR reactivation via MET/nMET. Emerging evidence suggests the possibility of nMET as a prognostic marker in relapsed cancer. This review summarizes recent findings about nMET and its unique role in recurrent cancer.

  1. Werken met taalportfolio's in het talenonderwijs aan volwassenen

    NARCIS (Netherlands)

    Broeder, P.; Sorce, M.R.

    2008-01-01

    Werken met portfolio’s is in het talenonderwijs (nog) een veelbelovend nieuw instrument om met leerlingen te werken aan taal. Met een taalportfolio kan de gebruiker de eigen taalkennis inschatten en bewijzen van zijn talenkennis verzamelen. Ook kan door het werken met een taalportfolio het verdere l

  2. Metáfora y novedad

    OpenAIRE

    Edeline, Francis

    2012-01-01

    Antes que nada, quisiera definirme como un semiótico cognoscitivo. Mi formación científica, por una parte, y mi pasado retórico en el sentido del Grupo μ, por otra, constituyen los puntos de partida de mi acercamiento al problema de la metáfora, que no podrá dejar de tocar, de paso, lo relazionado con el conocimiento, la cognición, el sentido.

  3. MET Standards for Electro-Technical Officers

    OpenAIRE

    Janusz Mindykowski

    2014-01-01

    The paper deals with one of the most important changes in the STCW 1978 as amended in 2010 Convention, from the point of view of the watchkeeping officers responsible for control, maintenance, diagnostic and repair of electrical and electronic installations on board of ships. Some reasons, why the MET Standards for Electro-Technical had to be developed and implemented are shortly analyzed and described. A legislative way towards and a short description of the minimum standards competence for ...

  4. Vice President Shen Wenqing Met JST Delegation

    Institute of Scientific and Technical Information of China (English)

    Zhang Yinglan

    2008-01-01

    @@ On May 19,2008,Prof.Shen Weqing,Vice President of NSFC,met with the delegation headed by Prof.Akira Fujishima,Director-General of China Research Center,Japan Science and Technology (JST).Prof.Fujishima is also the Chairman of Kanagawa Academy of Science and Technology,Japan and Foreign Member of the Chinese Academy of Sciences elected in 2003.

  5. Metáfora y estructura conceptual

    Directory of Open Access Journals (Sweden)

    Emilia Castaño

    2012-01-01

    Full Text Available La lingüística cognitiva siempre ha argumentado que la metáfora no pertenece exclusivamente al lenguaje, sino que es una competencia que se basa en la habilidad humana de concebir un dominio de experiencia en términos de otro. Entendida así, la metáfora no puede ser otra cosa que un fenómeno conceptual. No obstante, pocos adeptos de la lingüística cognitiva han concentrados sus esfuerzos en catalogar manifestaciones metafóricas en ámbitos no lingüísticos. En este trabajo, sugerimos que es factible encontrar pruebas de que la metáfora es un proceso conceptual y, como tal, se manifiesta en esferas que no son estrictamente lingüísticas. Para ello, aportamos un seguido de evidencias muy diversas, como por ejemplo su papel en el razonamiento lógico-matemático de los niños en la fase preoperacional del desarrollo cognitivo, la programación de interfaces para aplicaciones informáticas y los resultados de tres estudios empíricos realizados recientemente en el campo  de la psicología cognitiva que analizan los efectos whorfianos en la conceptualización del tiempo y los efectos del espacio en la memoria emocional.

  6. Mart Mets : "Mida rohkem ajaloolisi kihistusi, seda põnevam on aed" / Mart Mets

    Index Scriptorium Estoniae

    Mets, Mart

    2006-01-01

    Eesti elukutselisi aialoojaid tutvustavas sarjas vastab küsimustele maastikuarhitekt Mart Mets. M. Metsast, tema tähtsamad tööd. M. Mets endast, oma õpetajatest, lemmikstiilist, oma tulevasest aiast ja töödest, koostööst klientidega, uuselamurajoonide kruntide probleemidest, vana aia ümberkujundamisest, ilutaimedest, Eesti aiast jpm. Ill.: M. Metsa portreefoto, 6 ill. tema töödest

  7. Lack of influence of COMT and NET genes variants on executive functions in schizophrenic and bipolar patients, their first-degree relatives and controls

    OpenAIRE

    Szöke, Andrei; Schürhoff, Franck; Méary, Alexandre; Mathieu, Flavie; Chevalier, Fabien; Trandafir, Anca; Alter, Caroline; Roy, Isabelle; Bellivier, Franck; Leboyer, Marion

    2006-01-01

    Abnormal dopaminergic function in the prefrontal cortex (PFC) may be a key factor in the etiopathogeny of schizophrenia and bipolar disorder. Both schizophrenic and bipolar subjects have executive functions (EF) deficits, thought to reflect abnormal PFC function. The main inactivation pathways for dopamine in the PFC are enzymatic cleavage by the Carboxy-O-Methyl-Transferase (COMT) and reuptake by the nor-epinephrine transporter (NET). Our aim in this study was to replicate previous studies t...

  8. An association study of DRD2 and COMT polymorphisms with novelty seeking and harm avoidance scores, in two independent samples of depressed patients

    Directory of Open Access Journals (Sweden)

    Frampton Christopher MA

    2007-01-01

    Full Text Available Abstract Background It was recently reported that an interaction of the dopamine D2 receptor (DRD2 and catechol-O-methyltransferase (COMT influences the behavioural approach system – as measured using Carver and White's Behavioural Inhibition and Behavioural Approach System (BIS/BAS scales – in a sample of healthy German subjects. The Temperament and Character Inventory (TCI, in particular the novelty seeking (NS and harm avoidance (HA scales, correlates moderately with the BIS/BAS measure. This study aimed to examine support for an association of DRD2 and COMT with behavioural activation, using the TCI within two independent samples of depressed outpatients (for both samples n = 146. Methods Two clinical samples of depressed patients were ascertained to assess the efficacy of two different pharmacotherapy and psychotherapy treatments. Analysis of variance (ANOVA was used to analyse NS and HA scale and subscale scores with respect to gene loci within each clinical sample. Analysis of covariance were undertaken to examine the association of age and gender with NS and HA scores. An association of age group or gender with gene loci were explored using chi-squared tests, in each sample. Results No significant effect of DRD2 or COMT, either independently or as an interaction, on NS or HA scores was observed, within either sample. Whilst age was significantly negatively associated with NS scores, including age in the two- and three-way interactions did not affect the significance of the association of personality with gene loci. Conclusion This study suggests that the COMT-DRD2 Equilibrium Model of Positive Emotionality recently proposed by Reuter and his colleagues is not applicable amongst currently depressed individuals, whose behavioural approach and inhibition tendencies have been assessed using the TCI.

  9. Action of Halowax 1051 on Enzymes of Phase I (CYP1A1 and Phase II (SULT1A and COMT Metabolism in the Pig Ovary

    Directory of Open Access Journals (Sweden)

    Justyna Barć

    2013-01-01

    Full Text Available Polychlorinated naphthalenes (PCNs are a group of organochlorinated compounds exhibiting dioxin-like properties. Previously published data showed the direct action of PCN-rich Halowax 1051 on ovarian follicular steroidogenesis. Taking into consideration that the observed biological effects of PCNs may be frequently side effects of metabolites generated by their detoxification, the aim of this study was to determine the activity and expression of enzymes involved in phase I (cytochrome P450, family 1 (CYP1A1 and phase II (sulfotransferase (SULT1A and catechol-O-methyltransferase (COMT detoxification metabolism. Cocultures of granulosa and theca interna cells collected from sexually mature pigs were exposed to 1 pg/mL to 10 ng/mL of Halowax 1051 for 1 to 48 hours, after which levels and activities of CYP1A1, SULT1A, and COMT were measured. Dose-dependent increases of CYP1A1 activity and expression were observed. High doses of Halowax 1051 were inhibitory to COMT and SULT1A activity and reduced their protein levels. In conclusion, fast activation of phase I enzymes with simultaneous inhibition of phase II enzymes indicates that the previously observed effect of Halowax 1051 on follicular steroidogenesis may partially result from metabolite action occurring locally in ovarian follicles.

  10. The Met-allele of the BDNF Val66Met polymorphism enhances task switching in elderly.

    Science.gov (United States)

    Gajewski, Patrick D; Hengstler, Jan G; Golka, Klaus; Falkenstein, Michael; Beste, Christian

    2011-12-01

    In this study we examined the relevance of the functional brain-derived neurotrophic factor (BDNF) Val66Met polymorphism as a modulator of task-switching performance in healthy elderly by using behavioral and event-related potential (ERP) measures. Task switching was examined in a cue-based and a memory-based paradigm. Val/Val carriers were generally slower, showed enhanced reaction time variability and higher error rates, particularly during memory-based task switching than the Met-allele individuals. On a neurophysiological level these dissociative effects were reflected by variations in the N2 and P3 ERP components. The task switch-related N2 was increased while the P3 was decreased in Met-allele carriers, while the Val/Val genotype group revealed the opposite pattern of results. In cue-based task-switching no behavioral and ERP differences were seen between the genotypes. These data suggest that superior memory-based task-switching performance in elderly Met-allele carriers may emerge due to more efficient response selection processes. The results implicate that under special circumstances the Met-allele renders cognitive processes more efficient than the Val/Val genotype in healthy elderly, corroborating recent findings in young subjects.

  11. Targeting of the MET receptor tyrosine kinase by small molecule inhibitors leads to MET accumulation by impairing the receptor downregulation.

    Science.gov (United States)

    Leiser, Dominic; Pochon, Benoît; Blank-Liss, Wieslawa; Francica, Paola; Glück, Astrid A; Aebersold, Daniel M; Zimmer, Yitzhak; Medová, Michaela

    2014-03-03

    The MET receptor tyrosine kinase is deregulated primarily via overexpression or point mutations in various human cancers and different strategies for MET inhibition are currently evaluated in clinical trials. We observed by Western blot analysis and by Flow cytometry that MET inhibition by different MET small molecule inhibitors surprisingly increases in a dose-dependent manner total MET levels in treated cells. Mechanistically, this inhibition-related MET accumulation was associated with reduced Tyr1003 phosphorylation and MET physical association with the CBL ubiquitin ligase with concomitant decrease in MET ubiquitination. These data may suggest careful consideration for design of anti-MET clinical protocols. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  12. c-Met in chromophobe renal cell carcinoma.

    Science.gov (United States)

    Erlmeier, Franziska; Ivanyi, Philipp; Hartmann, Arndt; Autenrieth, Michael; Wiedemann, Max; Weichert, Wilko; Steffens, Sandra

    2017-02-01

    c-Met plays a role as a prognostic marker in clear cell renal cell carcinoma. In addition, recently the tyrosine kinase inhibitor cabozantinib targeting c-Met was approved for the treatment of advanced renal cell carcinoma (RCC). In contrast to clear cell RCC, little is known about c-Met expression patterns in rarer RCC subtypes. The aim of this study was to evaluate the prevalence, distribution and prognostic impact of c-Met expression on chromophobe (ch)RCC. Patients who underwent renal surgery due to chRCC were retrospectively evaluated. Tumor specimens were analyzed for c-Met expression by immunohistochemistry. Expression data were associated with clinicopathological parameters including patient survival. Eighty-one chRCC patients were eligible for analysis. Twenty-four (29.6%) patients showed a high c-Met expression (c-Met(high), staining intensity higher than median). Our results showed an association between c-Met(high) expression and the existence of lymph node metastasis (p = 0.007). No further significant clinicopathological associations with c-Met were identified, also regarding c-Met expression and overall survival. In conclusion, to our knowledge this is the first study evaluating the prognostic impact of c-Met in a considerably large cohort of chRCC. High c-Met expression is associated with the occurrence of lymph node metastasis. This indicates that c-Met might be implicated into metastatic progression in chRCC.

  13. Commonly-occurring polymorphisms in the COMT, DRD1 and DRD2 genes influence different aspects of motor sequence learning in humans.

    Science.gov (United States)

    Baetu, Irina; Burns, Nicholas R; Urry, Kristi; Barbante, Girolamo Giovanni; Pitcher, Julia B

    2015-11-01

    Performing sequences of movements is a ubiquitous skill that involves dopamine transmission. However, it is unclear which components of the dopamine system contribute to which aspects of motor sequence learning. Here we used a genetic approach to investigate the relationship between different components of the dopamine system and specific aspects of sequence learning in humans. In particular, we investigated variations in genes that code for the catechol-O-methyltransferase (COMT) enzyme, the dopamine transporter (DAT) and dopamine D1 and D2 receptors (DRD1 and DRD2). COMT and the DAT regulate dopamine availability in the prefrontal cortex and the striatum, respectively, two key regions recruited during learning, whereas dopamine D1 and D2 receptors are thought to be involved in long-term potentiation and depression, respectively. We show that polymorphisms in the COMT, DRD1 and DRD2 genes differentially affect behavioral performance on a sequence learning task in 161 Caucasian participants. The DRD1 polymorphism predicted the ability to learn new sequences, the DRD2 polymorphism predicted the ability to perform a previously learnt sequence after performing interfering random movements, whereas the COMT polymorphism predicted the ability to switch flexibly between two sequences. We used computer simulations to explore potential mechanisms underlying these effects, which revealed that the DRD1 and DRD2 effects are possibly related to neuroplasticity. Our prediction-error algorithm estimated faster rates of connection strengthening in genotype groups with presumably higher D1 receptor densities, and faster rates of connection weakening in genotype groups with presumably higher D2 receptor densities. Consistent with current dopamine theories, these simulations suggest that D1-mediated neuroplasticity contributes to learning to select appropriate actions, whereas D2-mediated neuroplasticity is involved in learning to inhibit incorrect action plans. However, the

  14. Volwassenen met overgewicht in beweging: de rol van de gezondheidsattitude

    NARCIS (Netherlands)

    Wouters, Eveline

    2008-01-01

    Factoren die mensen met overgewicht belemmeren om met een fysiek trainingsprogramma te beginnen Achtergrond: Bij overgewicht heeft lichaamsbeweging (bijvoorbeeld sportbeoefening) gunstige effecten op het behoud van gewicht(svermindering) en op verschillende aan overgewicht gerelateerde aandoeningen

  15. Samenwerking Wageningen UR met: Faculteit Diergeneeskunde Universiteit Utrecht

    NARCIS (Netherlands)

    Noorduyn, L.

    2008-01-01

    Wageningen UR werkt in haar onderzoeksprogramma’s samen met andere kennis - instellingen. Zo werkt Wageningen UR samen met de Universiteit van Utrecht bij het ontwikkelen van het welzijnsprogramma op het gebied van gezelschapsdieren

  16. Cloning and Analysis of Caffeic Acid O-methyltransferase Gene( SmCOMT1 ) from Salvia miltiorrhiza Bge.%丹参咖啡酸-O-甲基转移酶基因(SmCOMT1)的克隆及其分析

    Institute of Scientific and Technical Information of China (English)

    宋银; 王东浩; 吴锦斌; 周露; 王国栋; 王喆之

    2012-01-01

    According to the sequencing result of caffeic acid 0-methyltransferase from Salvia miltiorrhiza tran-scriptome database analysis, its specific primers were designed. By RT-PCR method, a novel COMT gene was i-solated from 5. miltiorrhiza, and named as SmCOMTl ( Genebank accession number; JF693491). SmCOMTl, with full-length cDNA of 1 158 bp, includes an open reading frame of 1 095 bp which encodes a 364 amino acids polypeptide. Furthermore, a length of 2 275 bp sequence was also cloned by PCR from genomic DNA of S. miltiorrhiza . The genomic DNA of SmCOMTl, aligned with cDNA, contains four exons and three introns in the encoding region. The results of amino acid sequence analysis shows that deduced amino acid polypeptide contains all the conserved element of COMT family and it is highly homologous to COMT proteins from the same family of Ocimum basilicum with 89% identity. Phylogenetic tree analysis also indicates that SmCOMTl is more related to the genetic relationship of COMT in dicotyledonous plants. Quantitative RT-PCR analysis revealed that SmCOMTl was expressed in different organs, and was highly expressed in stem, and could be induced by methyl jasmonate (MeJA) and pathogen. These results showed that SmCOMTl might be pathogen-responsive gene in plant defenses.%依据丹参转录组数据库得到的咖啡酸-O-甲基转移酶基因序列设计特异性引物,采用RT-PCR方法从丹参分离得到一个新的COMT基因,命名为SmCOMTI(GenBank注册号为JF693491).该基因cDNA全长1158 bp,包含一个长为1095 bp的开放阅读框,编码364个氨基酸.SmCOMT1 gDNA序列长2275 bp,包含4个外显子和3个内含子.序列分析结果表明,SmCOMT1编码的多肽具有COMT的序列保守元件,与同科植物罗勒COMT编码的多肽高度同源,同源性达到89%.系统进化树分析表明,SmCOMT1与双子叶植物的COMT亲缘关系较近.qRT-PCR 结果表明,SmCOMT1基因在丹参不同组织器官中差异表达,其中茎中的表达量最高,并

  17. Onderzoek naar de mutagene werking van methylacrylaat met microorganismen

    NARCIS (Netherlands)

    Voogd CE; van der Stel JJ; Verharen HW

    1984-01-01

    Met methylacrylaat is geen mutagene werking gevonden in de fluctuatietest met Klebsiella pneumoniae bij 0,02 mol/l (0,172% w/v) of minder in de vloeistoffase of bij 0,0002 mol/l (17,2 mg/l) of minder in de lucht. Met de Salmonella typhimurium stammen TA 98, TA 100 en TA 1535 is met methylacrylaat g

  18. MET Standards for Electro-Technical Officers

    Directory of Open Access Journals (Sweden)

    Janusz Mindykowski

    2014-12-01

    Full Text Available The paper deals with one of the most important changes in the STCW 1978 as amended in 2010 Convention, from the point of view of the watchkeeping officers responsible for control, maintenance, diagnostic and repair of electrical and electronic installations on board of ships. Some reasons, why the MET Standards for Electro-Technical had to be developed and implemented are shortly analyzed and described. A legislative way towards and a short description of the minimum standards competence for ETO are presented. Next, new tools supporting ETO’s standards implementation are appointed. Finally, the future works as well as the concluding remarks concerning discussed issue are formulated and commented on.

  19. Installing met towers in marine environments

    Energy Technology Data Exchange (ETDEWEB)

    Hanberg, Jackie [DNV Canada (Canada)

    2011-07-01

    Onshore measurements are taken to supplement offshore wind resource measurement campaigns. To maximize the quality of the measured data, the conditions presented by marine environments must be well understood and mitigated. This paper discusses the several factors that need attention prior to installation of the met towers. The towers experience high corrosion from their exposure to moist, salt-laden, marine air. Careful instrumentation and material selection can prevent or decrease corrosion. Stainless or galvanized hardware and coating sensor terminals with petroleum jelly are both helpful. Soil in the marine environment has variable moisture levels and is extremely wet, which makes grounding systems and backfill enhancers necessary. Weather conditions in these environments also tend to be unpredictable; hence, towers should be strong enough to handle typical marine weather. In conclusion, successful marine wind resource assessment campaigns require environmental research, careful planning, and awareness of the specific issues.

  20. Gevolgen nieuwe mineralen beleid : met aanvoernormen voor Telen met toekomst en BIOM bedrijven 6 bedrijven doorgerekend

    NARCIS (Netherlands)

    Wolf, de M.

    2004-01-01

    In 2006 gaat het nieuwe mestbeleid op basis van gebruiksnormen van start. In veel gevallen zullen de gebruiksnormen de totale aanvoer van mineralen sterker begrenzen dan Minas. PPO heeft voor een aantal Telen met Toekomst (TmT) en BIOM bedrijvendoorgerekend wat de gevolgen kunnen zijn.

  1. 'Gezond met haver' rapportage van het haverketenproject 'Gezond met haver' 2006-2008

    NARCIS (Netherlands)

    Gilissen, L.J.W.J.; Pinxterhuis, E.K.; Gremmen, H.G.J.

    2009-01-01

    In dit rapport wordt ingegaan op de resultaten en ervaringen van het project ‘Gezond met haver’. Het project betreft een innovatief Praktijkproject van TransForum. Het project is gestart in 2006 en afgerond in 2008. Het project heeft beoogd om een relevante bijdrage te leveren aan de maatschappelijk

  2. De eerste ervaringen van mensen met lichamelijke beperkingen met de Wmo.

    NARCIS (Netherlands)

    Klerk, M. de; Marangos, A.M.; Cardol, M.

    2009-01-01

    Op verzoek van het ministerie van Volksgezondheid, Welzijn en Sport (VWS) deed het SCP onderzoek naar de Wmo. Dit onderzoek bestaat uit twee sporen: onderzoek naar de effecten van de Wmo voor mensen met beperkingen en onderzoek naar gemeentelijk beleid. Onlangs verscheen een tussenrapport.

  3. Groei sturen en meer ruimte benutten met LED's in tulpenbroei (interview met Jeroen Wildschut)

    NARCIS (Netherlands)

    Bouwman-van Velden, P.; Wildschut, J.

    2010-01-01

    Bij blauw licht groeien tulpen omhoog en blijven langer dicht. Bij rood licht gaan ze hun blad juist spreiden. Lelies reageren heel anders. Het eerste oriënterende onderzoek met LED-belichting heeft aangetoond dat de kleuren van het licht straks mogelijk zijn in te zetten om de groei echt te sturen.

  4. Houtcomposities met glas, beton en kunststof. Onderzoeken TNO Bouw

    NARCIS (Netherlands)

    Kuilen, J.W.G. van de; Robson, D.J.

    1999-01-01

    TNO Bouw in Rijswijk probeert hout een meerwaarde te geven door het te combineren met andere materialen. De studies richten zich onder meer op de versterking van balken met vezels en van vloeren met een laag beton. Bovendien kijken de onderzoekers naar moge-lijkheden om afvalhout in kunststof te

  5. Gastrointestinal malignancies harbor actionable MET exon 14 deletions

    Science.gov (United States)

    Hong, Mineui; Kim, Sun Young; Jang, Jiryeon; Ahn, Soomin; Kang, So Young; Lee, Sujin; Kim, Seung Tae; Kim, Bogyou; Choi, Jaehyun; Kim, Kyung-Ah; Lee, Jiyun; Park, Charny; Park, Se Hoon; Park, Joon Oh; Lim, Ho Yeong; Kang, Won Ki; Park, Keunchil; Park, Young Suk; Kim, Kyoung-Mee

    2015-01-01

    Recently, MET exon 14 deletion (METex14del) has been postulated to be one potential mechanism for MET protein overexpression. We screened for the presence of METex14del transcript by multiplexed fusion transcript analysis using nCounter assay followed by confirmation with quantitative reverse transcription PCR with correlation to MET protein expression by immunohistochemistry (IHC) and MET amplification by fluorescence in situ hybridization (FISH). We extracted RNAs from 230 patients enrolled onto the prospective molecular profiling clinical trial (NEXT-1) (NCT02141152) between November 2013 and August 2014. Thirteen METex14del cases were identified including 3 gastric cancer, 4 colon cancer, 5 non-small cell lung cancer, and one adenocarcinoma of unknown primary. Of these 13 METex14del cases, 11 were MET IHC 3+ and 2 were 2+. Only one out of the 13 METex14del cases was MET amplified (MET/CEP ratio > 2.0). Growths of two (gastric, colon) METex14del+ patient tumor derived cell lines were profoundly inhibited by both MET tyrosine kinase inhibitors and a monoclonal antibody targeting MET. In conclusion, METex14del is a unique molecular aberration present in gastrointestinal (GI) malignancies corresponding with overexpression of MET protein but rarely with MET amplification. Substantial growth inhibition of METex14del+ patient tumor derived cell lines by several MET targeting drugs strongly suggests METex14del is a potential actionable driver mutation in GI malignancies. PMID:26375439

  6. Innoveren met serious games : Wat is serious gaming?

    NARCIS (Netherlands)

    Werkhoven, P.J.

    2008-01-01

    Het begrip serious gaming is inmiddels gekaapt door vele aanbieders van wat vroeger simulatie en virtual reality technologie genoemd werd. Met die technologie kunnen we mensen laten rondlopen in virtuele gebouwen en landschappen, al dan niet met grote projectieschermen of met brillen op. Maar dat is

  7. Revolutionising landscapes: Hydroelectricity and the heavy industrialisation of society and environment in the Comte de Beauharnois, 1927--1948

    Science.gov (United States)

    Pelletier, Louis-Raphael

    This dissertation analyses the rapid industrialisation of the rural Comte de Beauharnois and the adjacent stretch of the Fleuve Saint-Laurent owing to the construction, between 1929 and 1948, of a gigantic canal for hydroelectricity production and navigation by an electricity corporation called the Beauharnois Light Heat and Power (BLH&P). Using principally the archives of the BLH&P---especially its complaints files and its rich photographic record---this thesis argues that this process exemplifies the finance capitalist reorganisation of the society and ecosystems of the Canadian province of Quebec from the 19th century to the Great Depression. In keeping with recent work in environmental history, the transformation of rural landscapes and a river for heavy industry is described as an important dimension of a revolution in modes of production. More specifically, I argue that, in the case under study, the finance-capitalist reorganisation of Quebec revolved around two central and explicit projects, one social and the other environmental: the grouping of most individuals in an industrial working class without control over the means of production and the reorganisation of rural landscapes into reservoirs of modern energy and industrial natural resources.

  8. Association of catechol-o-methyl transferase gene polymorphism with prostate cancer and benign prostatic hyperplasia

    Directory of Open Access Journals (Sweden)

    mir davood omrani

    2009-08-01

    Full Text Available

    • BACKGROUND: A single nucleotide variation within  atechol-o-methyl transferase (COMT gene may alter the COMT enzyme activity level. Polymorphism of Val158Met in the COMT gene has been related to malignancy. In this regard, a study was carried out to find a possible association between the COMT gene polymorphism in patients with sporadic prostate cancer (PCa and benign prostatic hyperplasia (BPH.
    • METHODS: All types of COMT158 Val/Met polymorphism were carried out using ASO-PCR method in 41 patients with prostate cancer, 193 patients with benign prostatic hyperplasia and 107 healthy male individuals.
    • RESULTS: The results of this study showed that the frequency of low producer allele A at codon 158 of the  OMT gene is significantly different in BPH group compared to normal male control group (OR, 95% CI, p value 1.95: 1.46, 2.44, 0.021, respectively. However no significant difference was noticed when the comparison was made between prostate cancer group and normal male control group and also between BPH and PCa groups.
    • CONCLUSIONS: Decreased level of catechol-o-methyl transferase gene

    • Dopamine receptor D2 and catechol-O-methyltransferase gene polymorphisms associated with anorexia nervosa in Chinese Han population: DRD2 and COMT gene polymorphisms were associated with AN.

      Science.gov (United States)

      Peng, Sufang; Yu, Shunying; Wang, Qian; Kang, Qing; Zhang, Yanxia; Zhang, Ran; Jiang, Wenhui; Qian, Yiping; Zhang, Haiyin; Zhang, Mingdao; Xiao, Zeping; Chen, Jue

      2016-03-11

      Dopamine receptor D2 (DRD2) and catechol-O-methyltransferase (COMT) are important in dopamine system which is proved to be associated with food-anticipatory behavior, food restriction, reward and motivation. This has made them good candidates for anorexia nervosa (AN). The aim of this work is to explore the roles of DRD2 (rs1800497) and COMT (rs4680, rs4633, rs4818) gene polymorphisms in the susceptibility of AN within the Chinese Han population. We recruited 260AN patients with DSM-IV diagnosis criteria, and 247 unrelated, normal weight controls. DRD2 (rs1800497) and COMT (rs4680, rs4633, rs4818) were genotyped in all subjects. We found rs1800497 and rs4633 were associated with the susceptibility of AN within the Chinese Han sample, and allele C of rs1800497 was a protective factor. There was a gene-gene interaction between rs1800497 of DRD2 gene and rs4633 of COMT gene. We concluded that rs1800497 and rs4633 play important roles in the AN susceptibility with respect to the Chinese Han population. The gene-gene interaction between DRD2 and COMT contributes to the risk of AN.

    • MET: roles in epithelial-mesenchymal transition and cancer stemness

      Science.gov (United States)

      Jeon, Hye-Min

      2017-01-01

      In a number of cancers, deregulated MET pathway leads to aberrantly activated proliferative and invasive signaling programs that promote malignant transformation, cell motility and migration, angiogenesis, survival in hypoxia, and invasion. A better understanding of oncogenic MET signaling will help us to discover effective therapeutic approaches and to identify which tumors are likely to respond to MET-targeted cancer therapy. In this review, we will summarize the roles of MET signaling in cancer, with particular focus on epithelial-mesenchymal transition (EMT) and cancer stemness. Then, we will provide update on MET targeting agents and discuss the challenges that should be overcome for the development of an effective therapy. PMID:28164090

    • I. Estructuras metálicas ligeras

      Directory of Open Access Journals (Sweden)

      Beer, Hermann

      1967-09-01

      Full Text Available The first part of this paper is being published in the present issue of «Informes de la Construcción», and will be followed by two further parts in the next two numbers of this magazine. It corresponds to the manuscript utilised for the two lecturers given at Costillares by professor Hermann Beer. These lectures were given on March 8 and 9th last. Professor Beer, professor of the High Technical School of Graz, Austria, is President of the Committee II of A.I.P.C. and of the Committee VIII of the European Convention on Metallic Construction, and has worldwide reputation in the field of metallic structures. The up to date nature of the subject and the abundant graphical documentation which illustrates it has led this Institute to believe that it will be of great interest to professionals to publish the text of these lectures. It should be emphasized that professor Beer knows Spanish very well. He learnt this language during the years he was professor at the University of Tucumán, in Argentina. In the following text the Institute has only introduced some slight adjustments of syntax and spelling.Este trabajo, cuya primera parte se publica en este número y continuará y terminará en los dos próximos de INFORMES DE LA CONSTRUCCIÓN, corresponde al texto escrito por el propio conferenciante de las dos conferencias pronunciadas, en el aula de Costillares, por el profesor Hermann Beer, los días 8 y 9 de marzo pasado. El profesor Beer, Catedrático de la Escuela Técnica Superior de Graz (Austria, Presidente de la Comisión II de la A.I.P.C. y de la Comisión VIII de la Convención Europea de la Construcción Metálica, goza de una reputación universal en el campo de las estructuras metálicas. La actualidad del tema elegido para sus conferencias y la abundante documentación gráfica con que las ilustró, han hecho pensar al Instituto en el gran interés que, para los profesionales, pueda tener su publicación. Es de destacar que el profesor

    • Absence of tpr-met and expression of c-met in human gastric mucosa and carcinoma.

      Science.gov (United States)

      Heideman, D A; Snijders, P J; Bloemena, E; Meijer, C J; Offerhaus, G J; Meuwissen, S G; Gerritsen, W R; Craanen, M E

      2001-08-01

      The c-met proto-oncogene, encoding the hepatocyte growth factor receptor, can be activated by various mechanisms. These include, among others, gene amplification with concomitant overexpression and the tpr-met oncogenic rearrangement. In the case of gastric cancer, contradictory results on the presence of the tpr-met oncogenic rearrangement have been published. The current study aimed therefore to assess the prevalence of tpr-met expression in Caucasian gastric adenocarcinomas, to evaluate the importance of this oncogene in their carcinogenesis. In addition, the level of c-met expression was determined, to evaluate the role of this alternative mode of activation of the proto-oncogene. A series of Caucasian gastric adenocarcinomas (n=43) and normal gastric mucosal samples (n=14) was analysed for tpr-met and c-met expression. Expression of tpr-met mRNA in the samples was performed by two reverse transcriptase polymerase chain reaction (RT-PCR) assays, with excellent correlation. The specificity of both methods was confirmed by direct sequencing of the PCR products of the MNNG-HOS cell line, which is known to contain the rearrangement. The level of c-met expression was assessed using semi-quantitative RT-PCR assays and immunohistochemistry (IHC). None of the normal gastric mucosal or gastric adenocarcinoma samples expressed tpr-met mRNA, as determined by both RT-PCR assays. Seventy per cent of the adenocarcinomas showed overexpression of c-met, according to elevated c-met mRNA levels, compared with the expression level of normal gastric mucosa. A significant correlation was found between the level of c-met mRNA and protein expression. In conclusion, these results strongly suggest that tpr-met activation does not play a role in Caucasian gastric carcinogenesis, while overexpression of the c-met gene occurs in the majority of Caucasian gastric adenocarcinomas.

    • Polymorphisms in Phase I and Phase II genes and breast cancer risk and relations to persistent organic pollutant exposure: a case–control study in Inuit women

      Science.gov (United States)

      2014-01-01

      Background We have previously reported that chemicals belonging to the persistent organic pollutants (POPs) such as perfluorinated compounds (PFAS) and polychlorinated biphenyls (PCBs) are risk factors in Breast Cancer (BC) development in Greenlandic Inuit women. The present case–control study aimed to investigate the main effect of polymorphisms in genes involved in xenobiotic metabolism and estrogen biosynthesis, CYP1A1, CYP1B1, COMT and CYP17, CYP19 and the BRCA1 founder mutation in relation to BC risk and to explore possible interactions between the gene polymorphisms and serum POP levels on BC risk in Greenlandic Inuit women. Methods The study population consisted of 31 BC cases and 115 matched controls, with information on serum levels of POPs. Genotyping was conducted for CYP1A1 (Ile462Val; rs1048943), CYP1B1 (Leu432Val; rs1056836), COMT (Val158Met; rs4680), CYP17A1 (A1> A2; rs743572); CYP19A1 (C> T; rs10046) and CYP19A1 ((TTTA)n repeats) polymorphisms and BRCA1 founder mutation using TaqMan allelic discrimination method and polymerase chain reaction based restriction fragment length polymorphism. The χ2 –test was used to compare categorical variables between cases and controls and the odds ratios were estimated by unconditional logistic regression models. Results We found an independent association of CYP1A1 (Val) and CYP17 (A1) with BC risk. Furthermore, an increased BC risk was observed for women with high serum levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) and carriers of at least: one CYP1A1 variant Val allele; one variant COMT Met allele; or the common CYP17 A1 allele. No combined effects were seen between PFAS exposure and CYP1B1 and CYP19 polymorphisms. The risk of BC was not found significantly associated with exposure to PCBs and OCPs, regardless of genotype for all investigated SNPs. The frequency of the Greenlandic founder mutation in BRCA1 was as expected higher in cases than in controls. Conclusions The

    • 3D RoboMET Characterization

      Energy Technology Data Exchange (ETDEWEB)

      Madison, Jonathan D. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Susan, Donald F. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Kilgo, Alice C. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

      2015-10-01

      The goal of this project is to generate 3D microstructural data by destructive and non-destructive means and provide accompanying characterization and quantitative analysis of such data. This work is a continuing part of a larger effort to relate material performance variability to microstructural variability. That larger effort is called “Predicting Performance Margins” or PPM. In conjunction with that overarching initiative, the RoboMET.3D™ is a specific asset of Center 1800 and is an automated serialsectioning system for destructive analysis of microstructure, which is called upon to provide direct customer support to 1800 and non-1800 customers. To that end, data collection, 3d reconstruction and analysis of typical and atypical microstructures have been pursued for the purposes of qualitative and quantitative characterization with a goal toward linking microstructural defects and/or microstructural features with mechanical response. Material systems examined in FY15 include precipitation hardened 17-4 steel, laser-welds of 304L stainless steel, thermal spray coatings of 304L and geological samples of sandstone.

    • Over-expression of a human chromosome 22q11.2 segment including TXNRD2, COMT and ARVCF developmentally affects incentive learning and working memory in mice.

      Science.gov (United States)

      Suzuki, Go; Harper, Kathryn M; Hiramoto, Takeshi; Funke, Birgit; Lee, MoonSook; Kang, Gina; Buell, Mahalah; Geyer, Mark A; Kucherlapati, Raju; Morrow, Bernice; Männistö, Pekka T; Agatsuma, Soh; Hiroi, Noboru

      2009-10-15

      Duplication of human chromosome 22q11.2 is associated with elevated rates of mental retardation, autism and many other behavioral phenotypes. However, because duplications cover 1.5-6 Mb, the precise manner in which segments of 22q11.2 causally affect behavior is not known in humans. We have now determined the developmental impact of over-expression of an approximately 190 kb segment of human 22q11.2, which includes the genes TXNRD2, COMT and ARVCF, on behaviors in bacterial artificial chromosome (BAC) transgenic (TG) mice. BAC TG mice and wild-type (WT) mice were tested for their cognitive capacities, affect- and stress-related behaviors and motor activity at 1 and 2 months of age. An enzymatic assay determined the impact of BAC over-expression on the activity level of COMT. BAC TG mice approached a rewarded goal faster (i.e. incentive learning), but were impaired in delayed rewarded alternation during development. In contrast, BAC TG and WT mice were indistinguishable in rewarded alternation without delays, spontaneous alternation, prepulse inhibition, social interaction, anxiety-, stress- and fear-related behaviors and motor activity. Compared with WT mice, BAC TG mice had an approximately 2-fold higher level of COMT activity in the prefrontal cortex, striatum and hippocampus. These data suggest that over-expression of this 22q11.2 segment enhances incentive learning and impairs the prolonged maintenance of working memory, but has no apparent effect on working memory per se, affect- and stress-related behaviors or motor capacity. High copy numbers of this 22q11.2 segment might contribute to a highly selective set of phenotypes in learning and cognition during development.

    • COMT基因与精神分裂症的相关性及法医学意义%Association and Its Forensic Significance between COMT Gene and Schizophrenia

      Institute of Scientific and Technical Information of China (English)

      丁春丽; 周雪; 王保捷; 丁梅; 庞灏

      2012-01-01

      儿茶酚氧位甲基转移酶(catechol-O-methyltransferase,COMT)基因编码产生儿茶酚氧位甲基转移酶,该基因的遗传变异可能影响COMT的表达量及代谢活性,致使中枢神经系统的儿茶酚胺神经递质的有效浓度发生变化,导致中枢神经系统功能异常而与精神分裂症相关.本文对COMT基因的遗传多态性、遗传变异进行了综述,包括COMT基因的SNP、单倍型与精神分裂症的关系,与攻击或暴力行为的关系,与精神分裂症患者额叶认知功能的关系等.COMT基因遗传变异与精神分裂症患者攻击或暴力倾向的相关性研究对于司法精神病鉴定具有潜在的应用价值.%Catechol-O-methyltransferase(COMT) gene encodes catechol-O-methyltransferase, the variant of this gene may affect the expression and metabolic activity of COMT. As the result of the changes of the effective concentration of the catecholamine neurotransmitter in the central nervous system, central nervous system dysfunctions associated with schizophrenia. This review summarizes genetic polymorphism and diversity of COMT gene. It also elaborates the relation between SNP and haplotype of COMT gene and three aspects, which including schizophrenia, attacking and violent tendency, and the frontal cognitive function of the schizophreniac. The correlativity study between genetic variation of the COMT gene and schizophrenia in patients with attacking and violent tendency may be helpful for the assessment of forensic psychiatry.

    • Un roman pour la génération dot.com?: Le comte de Monte-Christo dans l'adaptation de Stephen Fry

      Directory of Open Access Journals (Sweden)

      Katarina Marinčič

      2010-12-01

      Full Text Available En 2000, le romancier britannique Stephen Fry publie The Starsʹ Tennis Balls, une adaptation modernisante du roman Le Comte de Monte-Cristo dʹAlexandre Dumas. Lʹobjectif de la présente contribution est dʹanalyser les techniques narratives des deux romanciers. Extrêmement fidèle au roman de Dumas au niveau de lʹintrigue, Stephen Fry sʹéloigne de son modèle au niveau stylistique, ce qui produit un effet de modernité qui ne sʹapparente pourtant pas à celui des adaptations cinématographiques.

    • Genetic polymorphisms in monoamine systems and outcome of cognitive behavior therapy for social anxiety disorder.

      Directory of Open Access Journals (Sweden)

      Evelyn Andersson

      Full Text Available OBJECTIVE: The role of genetics for predicting the response to cognitive behavior therapy (CBT for social anxiety disorder (SAD has only been studied in one previous investigation. The serotonin transporter (5-HTTLPR, the catechol-o-methyltransferase (COMT val158met, and the tryptophan hydroxylase-2 (TPH2 G-703T polymorphisms are implicated in the regulation of amygdala reactivity and fear extinction and therefore might be of relevance for CBT outcome. The aim of the present study was to investigate if these three gene variants predicted response to CBT in a large sample of SAD patients. METHOD: Participants were recruited from two separate randomized controlled CBT trials (trial 1: n = 112, trial 2: n = 202. Genotyping were performed on DNA extracted from blood or saliva samples. Effects were analyzed at follow-up (6 or 12 months after treatment for both groups and for each group separately at post-treatment. The main outcome measure was the Liebowitz Social Anxiety Scale Self-Report. RESULTS: At long-term follow-up, there was no effect of any genotype, or gene × gene interactions, on treatment response. In the subsamples, there was time by genotype interaction effects indicating an influence of the TPH2 G-703T-polymorphism on CBT short-term response, however the direction of the effect was not consistent across trials. CONCLUSIONS: None of the three gene variants, 5-HTTLPR, COMTval158met and TPH2 G-703T, was associated with long-term response to CBT for SAD. TRIAL REGISTRATION: ClinicalTrials.gov (ID-NCT0056496.

    • Targeting MET Amplification as a New Oncogenic Driver

      Energy Technology Data Exchange (ETDEWEB)

      Kawakami, Hisato [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Okamoto, Isamu, E-mail: okamotoi@kokyu.med.kyushu-u.ac.jp [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Center for Clinical and Translational Research, Kyushu University Hospital, 3-1-1 Maidashi, Higashiku, Fukuoka 812-8582 (Japan); Okamoto, Wataru [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Division of Transrlational Research, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577 (Japan); Tanizaki, Junko [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, HIM223, 450 Brookline Avenue, Boston, MA 02215 (United States); Nakagawa, Kazuhiko [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Nishio, Kazuto [Department of Genome Biology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan)

      2014-07-22

      Certain genetically defined cancers are dependent on a single overactive oncogene for their proliferation and survival, a phenomenon known as “oncogene addiction”. A new generation of drugs that selectively target such “driver oncogenes” manifests a clinical efficacy greater than that of conventional chemotherapy in appropriate genetically defined patients. MET is a proto-oncogene that encodes a receptor tyrosine kinase, and aberrant activation of MET signaling occurs in a subset of advanced cancers as result of various genetic alterations including gene amplification, polysomy, and gene mutation. Our preclinical studies have shown that inhibition of MET signaling either with the small-molecule MET inhibitor crizotinib or by RNA interference targeted to MET mRNA resulted in marked antitumor effects in cancer cell lines with MET amplification both in vitro and in vivo. Furthermore, patients with non-small cell lung cancer or gastric cancer positive for MET amplification have shown a pronounced clinical response to crizotinib. Accumulating preclinical and clinical evidence thus suggests that MET amplification is an “oncogenic driver” and therefore a valid target for treatment. However, the prevalence of MET amplification has not been fully determined, possibly in part because of the difficulty in evaluating gene amplification. In this review, we provide a rationale for targeting this genetic alteration in cancer therapy.

    • Mars MetNet Mission Pressure and Humidity Devices

      Science.gov (United States)

      Haukka, H.; Harri, A.-M.; Schmidt, W.; Genzer, M.; Polkko, J.; Kemppinen, O.; Leinonen, J.

      2012-09-01

      A new kind of planetary exploration mission for Mars is being developed in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission [1] is based on a new semi-hard landing vehicle called MetNet Lander (MNL). MetBaro and MetHumi are part of the scientific payload of the MNL. Main scientific goal of both devices is to measure the meteorological phenomena (pressure and humidity) of the Martian atmosphere and complement the previous Mars mission atmospheric measurements (Viking and Phoenix) for better understanding of the Martian atmospheric conditions.

  1. Targeting MET Amplification as a New Oncogenic Driver

    Directory of Open Access Journals (Sweden)

    Hisato Kawakami

    2014-07-01

    Full Text Available Certain genetically defined cancers are dependent on a single overactive oncogene for their proliferation and survival, a phenomenon known as “oncogene addiction”. A new generation of drugs that selectively target such “driver oncogenes” manifests a clinical efficacy greater than that of conventional chemotherapy in appropriate genetically defined patients. MET is a proto-oncogene that encodes a receptor tyrosine kinase, and aberrant activation of MET signaling occurs in a subset of advanced cancers as result of various genetic alterations including gene amplification, polysomy, and gene mutation. Our preclinical studies have shown that inhibition of MET signaling either with the small-molecule MET inhibitor crizotinib or by RNA interference targeted to MET mRNA resulted in marked antitumor effects in cancer cell lines with MET amplification both in vitro and in vivo. Furthermore, patients with non-small cell lung cancer or gastric cancer positive for MET amplification have shown a pronounced clinical response to crizotinib. Accumulating preclinical and clinical evidence thus suggests that MET amplification is an “oncogenic driver” and therefore a valid target for treatment. However, the prevalence of MET amplification has not been fully determined, possibly in part because of the difficulty in evaluating gene amplification. In this review, we provide a rationale for targeting this genetic alteration in cancer therapy.

  2. Effects of the BDNF Val66Met Polymorphism and Met Allele Load on Declarative Memory Related Neural Networks

    DEFF Research Database (Denmark)

    Dodds, Chris M; Henson, Richard N; Suckling, John;

    2013-01-01

    It has been suggested that the BDNF Val66Met polymorphism modulates episodic memory performance via effects on hippocampal neural circuitry. However, fMRI studies have yielded inconsistent results in this respect. Moreover, very few studies have examined the effect of met allele load on activation...... of memory circuitry. In the present study, we carried out a comprehensive analysis of the effects of the BDNF polymorphism on brain responses during episodic memory encoding and retrieval, including an investigation of the effect of met allele load on memory related activation in the medial temporal lobe....... In contrast to previous studies, we found no evidence for an effect of BDNF genotype or met load during episodic memory encoding. Met allele carriers showed increased activation during successful retrieval in right hippocampus but this was contrast-specific and unaffected by met allele load. These results...

  3. Oncogenic activation of the Met receptor tyrosine kinase fusion protein, Tpr-Met, involves exclusion from the endocytic degradative pathway.

    Science.gov (United States)

    Mak, H H L; Peschard, P; Lin, T; Naujokas, M A; Zuo, D; Park, M

    2007-11-01

    Multiple mechanisms of dysregulation of receptor tyrosine kinases (RTKs) are observed in human cancers. In addition to gain-of-function, loss of negative regulation also contributes to oncogenic activation of RTKs. Negative regulation of many RTKs involves their internalization and degradation in the lysosome, a process regulated through ubiquitination. RTK oncoproteins activated following chromosomal translocation, are no longer transmembrane proteins, and are predicted to escape lysosomal degradation. To test this, we used the Tpr-Met oncogene, generated following chromosomal translocation of the hepatocyte growth factor receptor (Met). Unlike Met, Tpr-Met is localized in the cytoplasm and also lacks the binding site for Cbl ubiquitin ligases. We determined whether subcellular localization of Tpr-Met, and/or loss of its Cbl-binding site, is important for oncogenic activity. Presence of a Cbl-binding site and ubiquitination of cytosolic Tpr-Met oncoproteins does not alter their transforming activity. In contrast, plasma membrane targeting allows Tpr-Met to enter the endocytic pathway, and Tpr-Met transforming activity as well as protein stability are decreased in a Cbl-dependent manner. We show that transformation by Tpr-Met is in part dependent on its ability to escape normal downregulatory mechanisms. This provides a paradigm for many RTK oncoproteins activated following chromosomal translocation.

  4. MET Expression in Primary and Metastatic Clear Cell Renal Cell Carcinoma: Implications of Correlative Biomarker Assessment to MET Pathway Inhibitors

    Directory of Open Access Journals (Sweden)

    Brian Shuch

    2015-01-01

    Full Text Available Aims. Inhibitors of the MET pathway hold promise in the treatment for metastatic kidney cancer. Assessment of predictive biomarkers may be necessary for appropriate patient selection. Understanding MET expression in metastases and the correlation to the primary site is important, as distant tissue is not always available. Methods and Results. MET immunofluorescence was performed using automated quantitative analysis and a tissue microarray containing matched nephrectomy and distant metastatic sites from 34 patients with clear cell renal cell carcinoma. Correlations between MET expressions in matched primary and metastatic sites and the extent of heterogeneity were calculated. The mean expression of MET was not significantly different between primary tumors when compared to metastases (P=0.1. MET expression weakly correlated between primary and matched metastatic sites (R=0.5 and a number of cases exhibited very high levels of discordance between these tumors. Heterogeneity within nephrectomy specimens compared to the paired metastatic tissues was not significantly different (P=0.39. Conclusions. We found that MET expression is not significantly different in primary tumors than metastatic sites and only weakly correlates between matched sites. Moderate concordance of MET expression and significant expression heterogeneity may be a barrier to the development of predictive biomarkers using MET targeting agents.

  5. Metástasis coroideas Choroidal metastases

    Directory of Open Access Journals (Sweden)

    C. Camarillo

    2008-01-01

    Full Text Available Las metástasis uveales son el tumor intraocular maligno más frecuente y de ellas, más del 80% se localizan en la coroides. Esto, unido al progresivo aumento de la incidencia, hace necesario su estudio y revisión para un correcto diagnóstico y tratamiento en la práctica clínica actual. La etiología varía según el sexo del paciente, siendo el carcinoma de pulmón el que con más frecuencia metastatiza en el varón y el de mama en la mujer. Tienden a la multifocalidad y generalmente se localizan en el polo posterior. En el 50% de los casos cursan de forma asintomática, pero pueden producir pérdida de visión, escotomas, metamorfopsias, y fotopsias. La exploración oftalmoscópica característica muestra una lesión coroidea placoide, homogénea y de aspecto cremoso. En el diagnóstico diferencial se debe considerar el nevus amelanótico, el melanoma amelanótico de coroides, el hemangioma coroideo, la escleritis posterior, el osteoma de coroides, las coriorretinitis, la enfermedad de Harada, el desprendimiento de retina rhegmatógeno, el síndrome de efusión uveal, y la coriorretinopatía serosa central. Una exhaustiva anamnesis y exploración oftalmológica completa son imprescindibles para el diagnóstico, a lo que se pueden añadir como pruebas complementarias la angiografía con fluoresceína, la ecografía ocular, la punción-aspiración con aguja fina (PAAF, la tomografía computarizada y la resonancia magnética. El tratamiento de estos tumores suele ser el tratamiento sistémico del tumor primario; las posibilidades de tratamiento local son la observación, la radioterapia externa, la braquiterapia, la termoterapia transpupilar y la enucleación.Uveal metastases are the most frequent malign intraocular tumour, of which more than 80% are localized in the choroids. This, together with the progressive increase in its incidence, makes its study and review necessary for a correct diagnosis and treatment in current clinical practice

  6. Epistatic interactions involving DRD2, DRD4, and COMT polymorphisms and risk of substance abuse in women with binge-purge eating disturbances.

    Science.gov (United States)

    Steiger, Howard; Thaler, Lea; Gauvin, Lise; Joober, Ridha; Labbe, Aurelie; Israel, Mimi; Kucer, Audrey

    2016-06-01

    Substance abuse is common in individuals with bulimia-spectrum (binge-purge) eating disturbances, a co-occurrence that has been attributed to shared neurobiological substrates--notably alterations in dopaminergic activity. We examined the implications of variations of selected, dopamine-relevant polymorphisms (DRD2 Taq1A, DRD4 7R, and COMT) for risk of substance abuse in women with binge-purge eating syndromes. We genotyped 183 women (66.1% showing full-threshold BN and 33.9% showing sub-syndromic variants), and assessed lifetime presence of alcohol, cannabis, cocaine, and stimulant abuse or dependence using structured interviews. Tests for main and interaction effects of various allele combinations revealed that individuals who carried high function COMT and low-function DRD4 7R alleles (a combination expected to be associated with higher risk) did indeed show more lifetime substance abuse and, specifically, more cannabis abuse. Our findings suggest that a gene combination that, in theory, codes for low levels of dopaminergic neurotransmission coincides with sensitivity to substance abuse in a sample displaying binge-purge eating-disorder variants.

  7. Virus-induced silencing of Comt, pAmt and Kas genes results in a reduction of capsaicinoid accumulation in chili pepper fruits.

    Science.gov (United States)

    del Rosario Abraham-Juárez, Ma; del Carmen Rocha-Granados, Ma; López, Mercedes G; Rivera-Bustamante, Rafael Francisco; Ochoa-Alejo, Neftalí

    2008-02-01

    Capsaicinoids are responsible for the pungent taste of chili pepper fruits of Capsicum species. Capsaicinoids are biosynthesized through both the phenylpropanoid and the branched-fatty acids pathways. Fragments of Comt (encoding a caffeic acid O-methyltransferase), pAmt (a putative aminotransferase), and Kas (a beta-keto-acyl-[acyl-carrier-protein] synthase) genes, that are differentially expressed in placenta tissue of pungent chili pepper, were individually inserted into a Pepper huasteco yellow veins virus (PHYVV)-derived vector to determine, by virus-induced gene silencing, irrespective of whether these genes are involved in the biosynthesis of capsaicinoids. Reduction of the respective mRNA levels as well as the presence of related siRNAs confirmed the silencing of these three genes. Morphological alterations were evident in plants inoculated with PHYVV::Comt and PHYVV::Kas constructs; however, plants inoculated with PHYVV::pAmt showed no evident alterations. On the other hand, fruit setting was normal in all cases. Biochemical analysis of placenta tissues showed that, indeed, independent silencing of all three genes led to a dramatic reduction in capsaicinoid content in the fruits demonstrating the participation of these genes in capsaicinoid biosynthesis. Using this approach it was possible to generate non-pungent chili peppers at high efficiency.

  8. Downsyndroom-kansbepaling met de eerstetrimestercombinatietest 2006-2008

    NARCIS (Netherlands)

    Schielen PCJI; Koster MPH; Elvers LH; Loeber JG; LIS

    2010-01-01

    Tussen 2006 en 2008 is 70 % van de zwangerschappen van een kind met downsyndroom correct voorspeld met de eerstetrimester-combinatietest. De test presteert daarmee iets minder dan in de vorige onderzochte periode, tussen 2004 en 2006. Het aantal aanvragen voor de test is in de onderzochte periode li

  9. Ringonderzoek : bepaling van coccidiostaticagehalte in diervoeders, met behulp van turbidimetrie

    NARCIS (Netherlands)

    Broex, N.J.G.; Huf, F.

    1988-01-01

    Voor de gehalte bepaling van monensin, salinomycine en narasin in diervoeders is de zg. turbidimetrische methode geringtest door 12 laboratoria. Ieder laboratorium heeft 9 monsters ontvangen, resp. 3 voormengsels en 6 diervoeders met monensin, salinomycine of narasin. De monsters zijn onderzocht met

  10. Wankel succes met druppelfertigatie in Franse prei : Op Proefboerderij Vredepeel

    NARCIS (Netherlands)

    Verstegen, S.; PPO Akkerbouw, Groene Ruimte en Vollegrondsgroente

    2007-01-01

    Bij PPO Vredepeel wordt in proeven prei geteeld met behulp van druppelfertigatie, met minder kunstmest en minder uitspoeling als doelen. In Frankrijk werken al sinds 2005 vijf preitelers in de streek Loire-Atlantique er mee op hun hele areaal. Eén van hen gebruikt 20 tot 40 procent minder kunst mest

  11. Massage bij verpleeghuisbewoners met ernstige dementie: een waardevolle interventie.

    NARCIS (Netherlands)

    Inhulsen, M.B.; Verkaik, R.; Busch, M.; Francke, A.

    2016-01-01

    Zorgverleners vinden dat massage een waardevolle bijdrage levert aan de zorg voor verpleeghuisbewoners met ernstige dementie. Met name in het maken van contact en het verminderen van onrust. Dit blijkt uit een pilot uitgevoerd door zorgorganisatie Laurens, het Van Praag Instituut en

  12. Alternatieve voedergewassen : ervaringen met erwten/graan, amarinth en snijsorghum

    NARCIS (Netherlands)

    Schooten, van H.A.

    2003-01-01

    In 2002 zijn door Praktijkonderzoek Veehouderij, in samenwerking met Stimuland Overijssel, drie demo's aangelegd met alternatieve voedergewassen voor de biologische melkveehouderij. De opbrengsten en voederwaarde-gegevens voor mengteelten gerst/erwten, gerst/rode klaver en triticale/erwten, en voor

  13. Efficacy of c-Met inhibitor for advanced prostate cancer

    Directory of Open Access Journals (Sweden)

    Christensen James G

    2010-10-01

    Full Text Available Abstract Background Aberrant expression of HGF/SF and its receptor, c-Met, often correlates with advanced prostate cancer. Our previous study showed that expression of c-Met in prostate cancer cells was increased after attenuation of androgen receptor (AR signalling. This suggested that current androgen ablation therapy for prostate cancer activates c-Met expression and may contribute to development of more aggressive, castration resistant prostate cancer (CRPC. Therefore, we directly assessed the efficacy of c-Met inhibition during androgen ablation on the growth and progression of prostate cancer. Methods We tested two c-Met small molecule inhibitors, PHA-665752 and PF-2341066, for anti-proliferative activity by MTS assay and cell proliferation assay on human prostate cancer cell lines with different levels of androgen sensitivity. We also used renal subcapsular and castrated orthotopic xenograft mouse models to assess the effect of the inhibitors on prostate tumor formation and progression. Results We demonstrated a dose-dependent inhibitory effect of PHA-665752 and PF-2341066 on the proliferation of human prostate cancer cells and the phosphorylation of c-Met. The effect on cell proliferation was stronger in androgen insensitive cells. The c-Met inhibitor, PF-2341066, significantly reduced growth of prostate tumor cells in the renal subcapsular mouse model and the castrated orthotopic mouse model. The effect on cell proliferation was greater following castration. Conclusions The c-Met inhibitors demonstrated anti-proliferative efficacy when combined with androgen ablation therapy for advanced prostate cancer.

  14. Aptamers Binding to c-Met Inhibiting Tumor Cell Migration.

    Directory of Open Access Journals (Sweden)

    Birgit Piater

    Full Text Available The human receptor tyrosine kinase c-Met plays an important role in the control of critical cellular processes. Since c-Met is frequently over expressed or deregulated in human malignancies, blocking its activation is of special interest for therapy. In normal conditions, the c-Met receptor is activated by its bivalent ligand hepatocyte growth factor (HGF. Also bivalent antibodies can activate the receptor by cross linking, limiting therapeutic applications. We report the generation of the RNA aptamer CLN64 containing 2'-fluoro pyrimidine modifications by systematic evolution of ligands by exponential enrichment (SELEX. CLN64 and a previously described single-stranded DNA (ssDNA aptamer CLN3 exhibited high specificities and affinities to recombinant and cellular expressed c-Met. Both aptamers effectively inhibited HGF-dependent c-Met activation, signaling and cell migration. We showed that these aptamers did not induce c-Met activation, revealing an advantage over bivalent therapeutic molecules. Both aptamers were shown to bind overlapping epitopes but only CLN3 competed with HGF binding to cMet. In addition to their therapeutic and diagnostic potential, CLN3 and CLN64 aptamers exhibit valuable tools to further understand the structural and functional basis for c-Met activation or inhibition by synthetic ligands and their interplay with HGF binding.

  15. Milde voedselverwerkingstechnologie II : milde conservering met hoge druk : nieuwe ontwikkelingen

    NARCIS (Netherlands)

    Matser, A.M.; Ven, van der C.; Berg, van den R.

    2004-01-01

    Met behulp van hogedruktechnologie kunnen producten langer houdbaar worden gemaakt. Deze bekende techniek kent de laatste tijd nieuwe ontwikkelingen en toepassingen . Naast pasteuriseren door een hogedrukbehandeling bij kamertemperatuur is het nu ook mogelijk om te steriliseren met hoge druk. Ook zi

  16. Massage bij verpleeghuisbewoners met ernstige dementie: een waardevolle interventie.

    NARCIS (Netherlands)

    Inhulsen, M.B.; Verkaik, R.; Busch, M.; Francke, A.

    2016-01-01

    Zorgverleners vinden dat massage een waardevolle bijdrage levert aan de zorg voor verpleeghuisbewoners met ernstige dementie. Met name in het maken van contact en het verminderen van onrust. Dit blijkt uit een pilot uitgevoerd door zorgorganisatie Laurens, het Van Praag Instituut en onderzoeksinstit

  17. Success, but Slowly, as Met School Redefines Learning

    Science.gov (United States)

    Pearson, George

    2012-01-01

    Seven Oaks Met School, the only high school in Canada that is part of the U.S.-based Big Picture Learning network of innovative schools, graduated its first class this spring. Internships with businesses and institutions in the community are a core element of the Met School experience. Students report on their internship experience, as well as on…

  18. Isolaatvorming en confessie in verband met de genetische bevolkingsstructuur

    NARCIS (Netherlands)

    1958-01-01

    In dit proefschrift is een onderzoek ingesteld bij een roomskatholieke enclave, gelegen in een gebied met een overwegend protestantse bevolking, in het noorden van de provincie Groningen in het noordelijkste deel van Nederland (Gemeente Leens). Door de beide bevolkingsgroepen met elkaar te vergelijk

  19. Influence of Genetic Variants in TPMT and COMT Associated with Cisplatin Induced Hearing Loss in Patients with Cancer : Two New Cohorts and a Meta-Analysis Reveal Significant Heterogeneity between Cohorts

    NARCIS (Netherlands)

    Hagleitner, Melanie M.; Coenen, Marieke J. H.; Patino-Garcia, Ana; de Bont, Eveline S. J. M.; Gonzalez-Neira, Anna; Vos, Hanneke I.; van Leeuwen, Frank N.; Gelderblom, Hans; Hoogerbrugge, Peter M.; Guchelaar, Henk-Jan; te Loo, Maroeska W. M.

    2014-01-01

    Treatment with cisplatin-containing chemotherapy regimens causes hearing loss in 40-60% of cancer patients. It has been suggested that genetic variants in the genes encoding thiopurine S-methyltransferase (TPMT) and catechol O-methyltransferase (COMT) can predict the development of cisplatin-induced

  20. Expression of cell wall related genes in basal and ear internodes of silking brown-midrib-3, caffeic acid O-methyltransferase (COMT down-regulated, and normal maize plants

    Directory of Open Access Journals (Sweden)

    Martinant Jean-Pierre

    2008-06-01

    Full Text Available Abstract Background Silage maize is a major forage and energy resource for cattle feeding, and several studies have shown that lignin content and structure are the determining factors in forage maize feeding value. In maize, four natural brown-midrib mutants have modified lignin content, lignin structure and cell wall digestibility. The greatest lignin reduction and the highest cell wall digestibility were observed in the brown-midrib-3 (bm3 mutant, which is disrupted in the caffeic acid O-methyltransferase (COMT gene. Results Expression of cell wall related genes was investigated in basal and ear internodes of normal, COMT antisens (AS225, and bm3 maize plants of the INRA F2 line. A cell wall macro-array was developed with 651 gene specific tags of genes specifically involved in cell wall biogenesis. When comparing basal (older lignifying and ear (younger lignifying internodes of the normal line, all genes known to be involved in constitutive monolignol biosynthesis had a higher expression in younger ear internodes. The expression of the COMT gene was heavily reduced, especially in the younger lignifying tissues of the ear internode. Despite the fact that AS225 transgene expression was driven only in sclerenchyma tissues, COMT expression was also heavily reduced in AS225 ear and basal internodes. COMT disruption or down-regulation led to differential expressions of a few lignin pathway genes, which were all over-expressed, except for a phenylalanine ammonia-lyase gene. More unexpectedly, several transcription factor genes, cell signaling genes, transport and detoxification genes, genes involved in cell wall carbohydrate metabolism and genes encoding cell wall proteins, were differentially expressed, and mostly over-expressed, in COMT-deficient plants. Conclusion Differential gene expressions in COMT-deficient plants highlighted a probable disturbance in cell wall assembly. In addition, the gene expressions suggested modified chronology of the

  1. A comparison of metabolic syndrome (MetS) risk factors in Filipino women and Filipino American women: a pilot study.

    Science.gov (United States)

    Ancheta, Irma B; Battie, Cynthia A; Tuason, Teresa; Ancheta, Christine V

    2012-01-01

    Cardiovascular disease (CVD) is a significant cause of morbidity and mortality in women of Filipino ethnicity. The objective of our work was to determine if metabolic syndrome (MetS), a modifiable CVD risk factor, differs in women as a function of country of residency and to determine if, CVD prevention strategies need to differ for these groups of Filipino women. Data were collected in community-based health screenings for this cross-sectional study. PARTICIPANTS were recruited at places of worship in southeast United States (n=60) and Central Visayas, Philippines (n=56). Prevalence of MetS and its component factors as defined by the International Diabetes Federation criteria. The prevalence of MetS in Filipino women (FW) and Filipino American women (FAW) groups was similar (52% vs 55%, P=.08) although the prevalence of elevated waist circumference was greater for FAW (78% vs 59%, P=.03). Conversely, the percentage of FW women with risk-associated high-density lipoprotein (HDL) levels was higher than the FAW group (84% vs 42%, P<.001). Other MetS component factors (blood pressure, glucose and triglycerides) did not significantly differ between groups. Similar high rates of MetS were observed in Filipino women regardless of the country of residency although the FAW tended to have higher rates of central obesity while the FW tended to have higher rates of risk-associated HDL levels. Further research should examine the cause of these differences in order to develop better cardiovascular screening and intervention strategies.

  2. Combinatie van walnoten met grasproductie en reactie : verslag van resultaten en ervaringen van de eerste jaren met 'Multifunctionele beplantingen', als bouwsteen voor meervoudig duurzaam landgebruik

    NARCIS (Netherlands)

    Oosterbaan, A.; Berg, van den C.A.; Valk, H.

    2003-01-01

    In de omgeving van Winterswijk is vanaf 1999 10 ha multifunctionele beplantingen aangelegd, hoofdzakelijk van walnoot met gras. Overhoeken zijn ingeplant met vruchtstruiken. De eerste ervaringen met aanplant, grasbeheer, bijdrage aan recreatie en dergelijke zijn in dit rapport weergegeven.

  3. MET and AKT genetic influence on facial emotion perception.

    Directory of Open Access Journals (Sweden)

    Ming-Teng Lin

    Full Text Available BACKGROUND: Facial emotion perception is a major social skill, but its molecular signal pathway remains unclear. The MET/AKT cascade affects neurodevelopment in general populations and face recognition in patients with autism. This study explores the possible role of MET/AKT cascade in facial emotion perception. METHODS: One hundred and eighty two unrelated healthy volunteers (82 men and 100 women were recruited. Four single nucleotide polymorphisms (SNP of MET (rs2237717, rs41735, rs42336, and rs1858830 and AKT rs1130233 were genotyped and tested for their effects on facial emotion perception. Facial emotion perception was assessed by the face task of Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT. Thorough neurocognitive functions were also assessed. RESULTS: Regarding MET rs2237717, individuals with the CT genotype performed better in facial emotion perception than those with TT (p = 0.016 by ANOVA, 0.018 by general linear regression model [GLM] to control for age, gender, and education duration, and showed no difference with those with CC. Carriers with the most common MET CGA haplotype (frequency = 50.5% performed better than non-carriers of CGA in facial emotion perception (p = 0.018, df = 1, F = 5.69, p = 0.009 by GLM. In MET rs2237717/AKT rs1130233 interaction, the C carrier/G carrier group showed better facial emotion perception than those with the TT/AA genotype (p = 0.035 by ANOVA, 0.015 by GLM, even when neurocognitive functions were controlled (p = 0.046 by GLM. CONCLUSIONS: To our knowledge, this is the first study to suggest that genetic factors can affect performance of facial emotion perception. The findings indicate that MET variances and MET/AKT interaction may affect facial emotion perception, implicating that the MET/AKT cascade plays a significant role in facial emotion perception. Further replication studies are needed.

  4. MetNet Precursor - Network Mission to Mars

    Science.gov (United States)

    Harri, Arri-Matti

    2010-05-01

    We are developing a new kind of planetary exploration mission for Mars - MetNet in situ observation network based on a new semi-hard landing vehicle called the Met-Net Lander (MNL). The first MetNet vehicle, MetNet Precursor, slated for launch in 2011. The MetNet development work started already in 2001. The actual practical Precursor Mission development work started in January 2009 with participation from various space research institutes and agencies. The scientific rationale and goals as well as key mission solutions will be discussed. The eventual scope of the MetNet Mission is to deploy some 20 MNLs on the Martian surface using inflatable descent system structures, which will be supported by observations from the orbit around Mars. Currently we are working on the MetNet Mars Precursor Mission (MMPM) to deploy one MetNet Lander to Mars in the 2011 launch window as a technology and science demonstration mission. The MNL will have a versatile science payload focused on the atmospheric science of Mars. Time-resolved in situ Martian meteorological measurements acquired by the Viking, Mars Pathfinder and Phoenix landers and remote sensing observations by the Mariner 9, Viking, Mars Global Surveyor, Mars Odyssey and the Mars Express orbiters have provided the basis for our current understanding of the behavior of weather and climate on Mars. However, the available amount of data is still scarce and a wealth of additional in situ observations are needed on varying types of Martian orography, terrain and altitude spanning all latitudes and longitudes to address microscale and mesoscale atmospheric phenomena. Detailed characterization of the Martian atmospheric circulation patterns and climatological cycles requires simultaneous in situ atmospheric observations. The scientific payload of the MetNet Mission encompasses separate instrument packages for the atmospheric entry and descent phase and for the surface operation phase. The MetNet mission concept and key probe

  5. Metáfora e transferência

    OpenAIRE

    2007-01-01

    O presente artigo tem como fito apontar em que sentido a transferência, no processo analítico, pode ser compreendida como metáfora. Utilizando o esquema gráfico construído por Searle (1995) para explicitar o processo que ocorre nas metáforas mortas, construímos uma analogia para compreender a transferência como uma metáfora morta (ainda que viva, no sentido de Lakoff e Johnson), que pode ser trazida para o plano da fala no campo analítico, ali onde o analista deve manter-se na ressonância de ...

  6. Higher FKBP5, COMT, CHRNA5, and CRHR1 allele burdens are associated with PTSD and interact with trauma exposure: implications for neuropsychiatric research and treatment

    Directory of Open Access Journals (Sweden)

    Boscarino JA

    2012-03-01

    Full Text Available Joseph A Boscarino1,2, Porat M Erlich1,3, Stuart N Hoffman4, Xiaopeng Zhang51Center for Health Research, Geisinger Clinic, Danville, PA, 2Department of Psychiatry, 3Department of Medicine, Temple University School of Medicine, Philadelphia, PA, 4Department of Neurology, 5Department of Anesthesiology, Geisinger Clinic, Danville, PA, USAObjective: The study aim was to assess the cumulative burden of polymorphisms located within four genetic loci previously associated with posttraumatic stress disorder (PTSD among outpatients at risk for PTSD.Methods: Diagnostic interviews were completed and DNA samples collected among 412 pain patients to determine if FKBP5 (rs9470080, COMT (rs4680, CHRNA5 (rs16969968, and CRHR1 (rs110402 single nucleotide polymorphisms were cumulatively associated with increased risk for PTSD.Results: In bivariate analyses, it was found that a count of specific PTSD risk alleles located within FKBP5, COMT, CHRNA5, and CRHR1 genetic loci (allele range = 0–6, mean count = 2.92, standard deviation = 1.36 was associated with lifetime (t [409] = 3.430, P = 0.001 and early onset PTSD (t [409] = 4.239, P = 0.000028. In logistic regression, controlling for demographic factors, personality traits, and trauma exposures, this risk allele count remained associated with both lifetime (odds ratio = 1.49, P = 0.00158 and early onset PTSD (odds ratio = 2.36, P = 0.000093. Interaction effects were also detected, whereby individuals with higher risk allele counts and higher trauma exposures had an increased risk of lifetime PTSD (allele count × high trauma, P = 0.026 and early onset PTSD (allele count × high trauma, P = 0.016 in these logistic regressions. Those with no or few risk alleles appeared resilient to PTSD, regardless of exposure history.Conclusion: A cumulative risk allele count involving four single nucleotide polymorphisms located within the FKBP5, COMT, CHRNA5, and CRHR1 genes are associated with PTSD. Level of trauma exposure

  7. Genetics of Lesch's typology of alcoholism.

    Science.gov (United States)

    Samochowiec, Jerzy; Kucharska-Mazur, Jolanta; Grzywacz, Anna; Pelka-Wysiecka, Justyna; Mak, Monika; Samochowiec, Agnieszka; Bienkowski, Przemyslaw

    2008-02-15

    It is widely accepted that dopamine and serotonin (5-HT) neurotransmission can be critically involved in the development of alcohol abuse and alcohol dependence. Lesch's typology of alcoholism has been gaining increasing popularity as it qualitatively differentiates patients into different treatment response subgroups. The aim of the present study was to evaluate a possible genetic background of Lesch's typology with special emphasis placed on dopamine- and serotonin-related genes. 122 alcoholics (the mean age: 35+/-9 years) were investigated. According to Lesch's typology, 58 patients were of type I, 36 patients of type II, 11 patients of type III, and 17 patients of type IV. Alcohol drinking and family history was assessed by means of a structured interview, based on the Semi-Structured Assessment for the Genetics of Alcoholism. 150 control subjects without psychiatric disorders were also recruited. The control group was ethnically-, age- and gender-matched to the patients. The DRD2 TaqIA, exon 8, and promoter -141C ins/del polymorphisms as well as COMT Val158Met, 5HTT 44 bp del in promoter, and DAT 40 bp VNTR polymorphisms were detected by means of PCR. No significant differences were observed when the whole group of alcoholics and the controls were compared. Similarly, there were no differences between either the Lesch type I or type II alcoholics and the control subjects. No significant differences were observed between type I and type II alcoholics. Alleles frequencies were not calculated for the Lesch type III and type IV alcoholics since the number of patients was too small. The present results argue against any major role of the investigated polymorphisms in either Lesch type I or type II alcoholism. More comprehensive studies are needed to define the role of the investigated polymorphisms in Lesch type III and type IV alcoholism.

  8. Association between dopamine-related polymorphisms and plasma concentrations of prolactin during risperidone treatment in schizophrenic patients.

    Science.gov (United States)

    Yasui-Furukori, Norio; Saito, Manabu; Tsuchimine, Shoko; Nakagami, Taku; Sato, Yasushi; Sugawara, Norio; Kaneko, Sunao

    2008-08-01

    Hyperprolactinemia is an inevitable consequence of treatment with antipsychotic agents to some extent because prolactin response to antipsychotics is related to dopamine blockade. Recent studies have suggested that polymorphisms of the dopamine receptors are associated with therapeutic response to antipsychotics. Thus, we studied the effects of major polymorphisms of dopamine-related genes on plasma concentration of prolactin. Subjects were 174 schizophrenic patients (68 males, 106 females) receiving 3 mg twice daily of risperidone for at least 4 weeks. Sample collections were conducted 12 h after the bedtime dosing. Five dopamine-related polymorphisms (Taq1A, -141C ins/del for DRD2, Ser9Gly for DRD3, 48 bp VNTR for DRD4, Val158Met for COMT) were identified. The mean (+/-SD) plasma concentration of prolactin in females was significantly higher than males (54.3+/-27.2 ng/ml versus 126.8+/-70.2 ng/ml, p<0.001). No dopamine-related polymorphisms differed the plasma concentration of prolactin in males or females. Multiple regression analyses including plasma drug concentration and age revealed that plasma concentration of prolactin correlated with gender (standardized partial correlation coefficients (beta)=0.551, p<0.001) and negatively with age (standardized beta=-0.202, p<0.01). No correlations were found between prolactin concentration and dopamine-related polymorphisms. These findings suggest that plasma prolactin concentrations in females are much higher than in males but the dopamine-related variants are not predominantly associated with plasma concentration of prolactin.

  9. Individual Differences in the Speed of Facial Emotion Recognition Show Little Specificity but Are Strongly Related with General Mental Speed: Psychometric, Neural and Genetic Evidence.

    Science.gov (United States)

    Liu, Xinyang; Hildebrandt, Andrea; Recio, Guillermo; Sommer, Werner; Cai, Xinxia; Wilhelm, Oliver

    2017-01-01

    Facial identity and facial expression processing are crucial socio-emotional abilities but seem to show only limited psychometric uniqueness when the processing speed is considered in easy tasks. We applied a comprehensive measurement of processing speed and contrasted performance specificity in socio-emotional, social and non-social stimuli from an individual differences perspective. Performance in a multivariate task battery could be best modeled by a general speed factor and a first-order factor capturing some specific variance due to processing emotional facial expressions. We further tested equivalence of the relationships between speed factors and polymorphisms of dopamine and serotonin transporter genes. Results show that the speed factors are not only psychometrically equivalent but invariant in their relation with the Catechol-O-Methyl-Transferase (COMT) Val158Met polymorphism. However, the 5-HTTLPR/rs25531 serotonin polymorphism was related with the first-order factor of emotion perception speed, suggesting a specific genetic correlate of processing emotions. We further investigated the relationship between several components of event-related brain potentials with psychometric abilities, and tested emotion specific individual differences at the neurophysiological level. Results revealed swifter emotion perception abilities to go along with larger amplitudes of the P100 and the Early Posterior Negativity (EPN), when emotion processing was modeled on its own. However, after partialling out the shared variance of emotion perception speed with general processing speed-related abilities, brain-behavior relationships did not remain specific for emotion. Together, the present results suggest that speed abilities are strongly interrelated but show some specificity for emotion processing speed at the psychometric level. At both genetic and neurophysiological levels, emotion specificity depended on whether general cognition is taken into account or not. These

  10. Individual Differences in the Speed of Facial Emotion Recognition Show Little Specificity but Are Strongly Related with General Mental Speed: Psychometric, Neural and Genetic Evidence

    Directory of Open Access Journals (Sweden)

    Xinyang Liu

    2017-08-01

    Full Text Available Facial identity and facial expression processing are crucial socio-emotional abilities but seem to show only limited psychometric uniqueness when the processing speed is considered in easy tasks. We applied a comprehensive measurement of processing speed and contrasted performance specificity in socio-emotional, social and non-social stimuli from an individual differences perspective. Performance in a multivariate task battery could be best modeled by a general speed factor and a first-order factor capturing some specific variance due to processing emotional facial expressions. We further tested equivalence of the relationships between speed factors and polymorphisms of dopamine and serotonin transporter genes. Results show that the speed factors are not only psychometrically equivalent but invariant in their relation with the Catechol-O-Methyl-Transferase (COMT Val158Met polymorphism. However, the 5-HTTLPR/rs25531 serotonin polymorphism was related with the first-order factor of emotion perception speed, suggesting a specific genetic correlate of processing emotions. We further investigated the relationship between several components of event-related brain potentials with psychometric abilities, and tested emotion specific individual differences at the neurophysiological level. Results revealed swifter emotion perception abilities to go along with larger amplitudes of the P100 and the Early Posterior Negativity (EPN, when emotion processing was modeled on its own. However, after partialling out the shared variance of emotion perception speed with general processing speed-related abilities, brain-behavior relationships did not remain specific for emotion. Together, the present results suggest that speed abilities are strongly interrelated but show some specificity for emotion processing speed at the psychometric level. At both genetic and neurophysiological levels, emotion specificity depended on whether general cognition is taken into account

  11. Individual Differences in the Speed of Facial Emotion Recognition Show Little Specificity but Are Strongly Related with General Mental Speed: Psychometric, Neural and Genetic Evidence

    Science.gov (United States)

    Liu, Xinyang; Hildebrandt, Andrea; Recio, Guillermo; Sommer, Werner; Cai, Xinxia; Wilhelm, Oliver

    2017-01-01

    Facial identity and facial expression processing are crucial socio-emotional abilities but seem to show only limited psychometric uniqueness when the processing speed is considered in easy tasks. We applied a comprehensive measurement of processing speed and contrasted performance specificity in socio-emotional, social and non-social stimuli from an individual differences perspective. Performance in a multivariate task battery could be best modeled by a general speed factor and a first-order factor capturing some specific variance due to processing emotional facial expressions. We further tested equivalence of the relationships between speed factors and polymorphisms of dopamine and serotonin transporter genes. Results show that the speed factors are not only psychometrically equivalent but invariant in their relation with the Catechol-O-Methyl-Transferase (COMT) Val158Met polymorphism. However, the 5-HTTLPR/rs25531 serotonin polymorphism was related with the first-order factor of emotion perception speed, suggesting a specific genetic correlate of processing emotions. We further investigated the relationship between several components of event-related brain potentials with psychometric abilities, and tested emotion specific individual differences at the neurophysiological level. Results revealed swifter emotion perception abilities to go along with larger amplitudes of the P100 and the Early Posterior Negativity (EPN), when emotion processing was modeled on its own. However, after partialling out the shared variance of emotion perception speed with general processing speed-related abilities, brain-behavior relationships did not remain specific for emotion. Together, the present results suggest that speed abilities are strongly interrelated but show some specificity for emotion processing speed at the psychometric level. At both genetic and neurophysiological levels, emotion specificity depended on whether general cognition is taken into account or not. These

  12. Leren met behulp van strategieën

    NARCIS (Netherlands)

    Reijners, Pauline; Kester, Liesbeth; Wetzels, Sandra; Kirschner, Paul A.

    2012-01-01

    Reijners, P. B. G., Kester, L., Wetzels, S. A. J., & Kirschner, P. A. (2012, 9 March). Leren met behulp van strategieën. Presentation at mini conference 'The Testing Effect' from the master programme Learning Sciences, Eindhoven, The Netherlands.

  13. Skills Labs: Hoogwaardige e-practica Water Management met EMERGO

    NARCIS (Netherlands)

    Nadolski, Rob; Hummel, Hans; Slootmaker, Aad; Kurvers, Hub

    2010-01-01

    Nadolski, R. J., Hummel, H. G. K., Slootmaker, A., & Kurvers, H. (2010, 27 May). Skills Labs: Hoogwaardige e-practica Water Management met EMERGO. Presentatie tijdens de bijeenkomst: Surfen door Zeeland: e-learning delta innovaties, Vlissingen, Nederland. SURFFoundation.

  14. c-Met in pancreatic cancer stem cells: Therapeutic implications

    Institute of Scientific and Technical Information of China (English)

    Marta Herreros-Villanueva; Aizpea Zubia-Olascoaga; Luis Bujanda

    2012-01-01

    Pancreatic cancer is the deadliest solid cancer and currently the fourth most frequent cause of cancer-related deaths.Emerging evidence suggests that cancer stem cells (CSCs) play a crucial role in the development and progression of this disease.The identification of CSC markers could lead to the development of new therapeutic targets.In this study,the authors explore the functional role of c-Met in pancreatic CSCs,by analyzing self-renewal with sphere assays and tumorigenicity capacity in NOD SCID mice.They concluded that c-Met is a novel marker for identifying pancreatic CSCs and c-Methigh in a higher tumorigenic cancer cell population.Inhibition of c-Met with XL184 blocks self-renewal capacity in pancreatic CSCs.In pancreatic tumors established in NOD SCID mice,c-Met inhibition slowed tumor growth and reduced the population of CSCs,along with preventing the development of metastases.

  15. Onderzoek leert ook van praktijk : telen met toekomst

    NARCIS (Netherlands)

    Kool, de S.A.M.; Dwarswaard, A.

    2002-01-01

    Het project 'Telen met toekomst' is een leerproces van zowel de onderzoeker als de teler. In zes jaar gaan deelnemers na wat technisch en economisch mogelijk is om het gebruik van mineralen, gewasbeschermingmiddelen en energie terug te dringen

  16. Met flora meer fauna de stad in trekken

    NARCIS (Netherlands)

    Hoffman, M.H.A.

    2010-01-01

    Meer flora en fauna in de stedelijke omgeving begint met de aanplant van gevarieerd groen. Plant Publicity Holland geeft in een overzicht aan welke bomen, heesters en vaste planten daarvoor geschikt zijn.

  17. Samenwerking Wageningen UR met BayerCropScience

    NARCIS (Netherlands)

    Wijsmuller, J.

    2010-01-01

    Wageningen UR werkt in haar onderzoeksprogramma’s samen met andere kennisinstellingen. In dit artikel een nadere kennismaking meteen van deze partners: Bayer CropsScience. Bayer CropScience ontwikkelt bestrijdingsmiddelen voor de Nederlandse markt.

  18. Mars MetNet Mission - Martian Atmospheric Observational Post Network

    Science.gov (United States)

    Hari, Ari-Matti; Haukka, Harri; Aleksashkin, Sergey; Arruego, Ignacio; Schmidt, Walter; Genzer, Maria; Vazquez, Luis; Siikonen, Timo; Palin, Matti

    2017-04-01

    A new kind of planetary exploration mission for Mars is under development in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semi-hard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor [1] mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide significant insights in to the Martian atmospheric behavior. The key technologies of the MetNet Lander have been qualified and the electrical qualification model (EQM) of the payload bay has been built and successfully tested. 1. MetNet Lander The MetNet landing vehicles are using an inflatable entry and descent system instead of rigid heat shields and parachutes as earlier semi-hard landing devices have used. This way the ratio of the payload mass to the overall mass is optimized. The landing impact will burrow the payload container into the Martian soil providing a more favorable thermal environment for the electronics and a suitable orientation of the telescopic boom with external sensors and the radio link antenna. It is planned to deploy several tens of MNLs on the Martian surface operating at least partly at the same time to allow meteorological network science. 2. Strawman Scientific Payload The strawman payload of the two MNL precursor models includes the following instruments: Atmospheric instruments: - MetBaro Pressure device - MetHumi Humidity device - MetTemp Temperature sensors Optical devices: - PanCam Panoramic - MetSIS Solar irradiance sensor with OWLS optical wireless system for data transfer - DS Dust sensor Composition and Structure Devices: Tri-axial magnetometer MOURA Tri-axial System Accelerometer The descent processes dynamic properties are monitored by a special 3-axis

  19. Loss of embryonic MET signaling alters profiles of hippocampal interneurons.

    Science.gov (United States)

    Martins, Gabriela J; Plachez, Céline; Powell, Elizabeth M

    2007-01-01

    Hippocampal interneurons arise in the ventral forebrain and migrate dorsally in response to cues, including hepatocyte growth factor/scatter factor which signals via its receptor MET. Examination of the hippocampus in adult mice in which MET had been inactivated in the embryonic proliferative zones showed an increase in parvalbumin-expressing cells in the dentate gyrus, but a loss of these cells in the CA3 region. An overall loss of calretinin-expressing cells was seen throughout the hippocampus. A similar CA3 deficit of parvalbumin and calretinin cells was observed when MET was eliminated only in postmitotic cells. These data suggest that MET is required for the proper hippocampal development, and embryonic perturbations lead to long-term anatomical defects with possible learning and memory dysfunction.

  20. Nieuw Zorgaanbod: Gesloten jeugdzorg voor adolescenten met ernstige gedragsproblemen

    NARCIS (Netherlands)

    Nijhof, K.S.; Dam, C. van; Veerman, J.W.; Engels, R.C.M.E.; Scholte, R.H.J.

    2010-01-01

    Tot voor kort werd een toenemend aantal jongeren met ernstige gedragsproblemen in jeugdgevangenissen geplaatst. Deze jongeren, ook wel ‘civielrechtelijke’ jongeren genoemd, werden niet geplaatst vanwege veroordelingen voor criminele activiteiten, maar omdat zij beschermd dienden te worden tegen zich

  1. MMPM - Mission implementation of Mars MetNet Precursor

    Science.gov (United States)

    Harri, A.-M.

    2009-04-01

    We are developing a new kind of planetary exploration mission for Mars - MetNet in situ observation network based on a new semi-hard landing vehicle called the Met-Net Lander (MNL). The key technical aspects and solutions of the mission will be discussed. The eventual scope of the MetNet Mission is to deploy some 20 MNLs on the Martian surface using inflatable descent system structures, which will be supported by observations from the orbit around Mars. Currently we are working on the MetNet Mars Precursor Mission (MMPM) to deploy one MetNet Lander to Mars in the 2009/2011 launch window as a technology and science demonstration mission. The MNL will have a versatile science payload focused on the atmospheric science of Mars. Detailed characterization of the Martian atmospheric circulation patterns, boundary layer phenomena, and climatology cycles, require simultaneous in-situ measurements by a network of observation posts on the Martian surface. The scientific payload of the MetNet Mission encompasses separate instrument packages for the atmospheric entry and descent phase and for the surface operation phase. The MetNet mission concept and key probe technologies have been developed and the critical subsystems have been qualified to meet the Martian environmental and functional conditions. This development effort has been fulfilled in collaboration between the Finnish Meteorological Institute (FMI), the Russian Lavoschkin Association (LA) and the Russian Space Research Institute (IKI) since August 2001. Currently the INTA (Instituto Nacional de Técnica Aeroespacial) from Spain is also participating in the MetNet payload development.

  2. Metsänomistajien suhtautuminen suometsien hoidon kokonaispalveluun Pirkanmaan alueella

    OpenAIRE

    Viitanen, Matti

    2012-01-01

    Metsäojituksia on Suomen maaperällä tehty jo toistasataa vuotta. Tänä aikana uudisojittamisesta on siirrytty jo ojitettujen suometsien kunnostuksiin. Vaikka monille metsistään huolehtiminen on sydämen asia, toisaalla hakkuukypsiä metsiköitä lahoaa hiljalleen luonnontilaiseksi ennallistuviin suometsiin. Kunnostamattomien tai mahdollisesti vuosikymmeniä sitten edellisen kerran käsiteltyjen ojitusalueiden kartoittaminen ja kunnostaminen tarjoavat metsänomistajalle hyvän tilaisuuden reali...

  3. Association study of single nucleotide polymorphism rs165599 of COMT gene, with schizophrenia and bipolar mood disorder in the south-west of Iran

    Directory of Open Access Journals (Sweden)

    Parisima Behbahani

    2015-06-01

    Full Text Available Linkage studies and epidemiological findings indicate that some possible genes in schizophrenia (SCZ and bipolar mood disorder (BPD are common. Numerous evidences for linkage of two diseases on chromosome 22 have been found. These findings suggest that one or more genes in the 22q11.21 region may be involved in the development of both disorders. In the present case-control study, association between the mentioned disorders and a genetic polymorphism (rs165599 of catechol O-methyltransferase (COMT, OMIM: 116790 was studied. Here 100 BPD patients, 100 SCZ patients, and 100 healthy controls were included in the study. The samples were matched in terms of gender and ethnicity. Statistical analysis showed that there was a significant association this polymorphism and risk of SCZ. The AG (OR=7.41, 95% CI: 3.21-17.1, P

  4. Robert LEROUX, Aux fondements de l’industrialisme. Comte, Dunoyer et la pensée libérale en France

    OpenAIRE

    Pranchère, Jean-Yves

    2016-01-01

    L’objectif affiché par l’ouvrage de Robert Leroux est de « combler une importante lacune » de l’histoire des idées (p. 10). Le but est atteint et on ne peut que se féliciter de disposer d’une présentation synthétique – à la fois érudite et accessible aux non-spécialistes – d’un courant trop oublié du libéralisme français : celui de Charles Comte (1782-1837) et de Charles Dunoyer (1786-1862), qui donnèrent au mot de « libéral » son sens classique en récusant les tendances étatistes de la pensé...

  5. Mars MetNet Mission - Martian Atmospheric Observational Post Network

    Science.gov (United States)

    Harri, Ari-Matti; Aleksashkin, Sergey; Arruego, Ignacio; Schmidt, Walter; Ponomarenko, Andrey; Apestigue, Victor; Genzer, Maria; Vazquez, Luis; Uspensky, Mikhail; Haukka, Harri

    2016-04-01

    A new kind of planetary exploration mission for Mars is under development in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semi-hard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor [1] mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide significant insights in to the Martian atmospheric behavior. The key technologies of the MetNet Lander have been qualified and the electrical qualification model (EQM) of the payload bay has been built and successfully tested. MetNet Lander The MetNet landing vehicles are using an inflatable entry and descent system instead of rigid heat shields and parachutes as earlier semi-hard landing devices have used. This way the ratio of the payload mass to the overall mass is optimized. The landing impact will burrow the payload container into the Martian soil providing a more favorable thermal environment for the electronics and a suitable orientation of the telescopic boom with external sensors and the radio link antenna. It is planned to deploy several tens of MNLs on the Martian surface operating at least partly at the same time to allow meteorological network science. Strawman Scientific Payload The strawman payload of the two MNL precursor models includes the following instruments: Atmospheric instruments: • MetBaro Pressure device • MetHumi Humidity device • MetTemp Temperature sensors Optical devices: • PanCam Panoramic • MetSIS Solar irradiance sensor with OWLS optical wireless system for data transfer • DS Dust sensor Composition and Structure Devices: • Tri-axial magnetometer MOURA • Tri-axial System Accelerometer The descent processes dynamic properties are monitored by a special

  6. Intersectorale samenwerking in de biologische landbouw : mengvoergrondstoffen met binnen- of buitenlandse oorsprong: effect op energieverbruik met mengvoerproductie

    NARCIS (Netherlands)

    Bos, J.F.F.P.

    2006-01-01

    Plant Research International (PRI) gaat in het rapport 'Mengvoergrondstoffen met binnen- of buitenlandse oorsprong: effect op energieverbruik van mengvoerproductie' in op het energieverbruik van de productie van enkele mengvoeders voor biologisch gehouden vleesvarkens. De onderzochte mengvoeders ver

  7. Greguerías - da metáfora literária à metáfora visual

    OpenAIRE

    Amador, Constança Araújo

    2014-01-01

    A presente investigação visa a passagem da metáfora literária para a metáfora visual, através do resultado de um trabalho de ilustração, tendo como ponto de partida, as Greguerías de Ramón Gómez de la Serna (1888 - 1963). Reflectindo sobre a interpretação da metáfora, o objectivo passa por criar uma nova selecção de Greguerías ilustradas que também estabeleçam novas metáforas visuais, a partir da sua interacção com a palavra. Mas uma vez independentes, cada ilustração ou cada conjunto d...

  8. Mars MetNet Mission - Martian Atmospheric Observational Post Network

    Science.gov (United States)

    Haukka, Harri; Harri, Ari-Matti; Aleksashkin, Sergey; Arruego, Ignacio; Schmidt, Walter; Genzer, Maria; Vazquez, Luis; Siikonen, Timo; Palin, Matti

    2016-10-01

    A new kind of planetary exploration mission for Mars is under development in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semi-hard landing vehicle called MetNet Lander (MNL).The scientific payload of the Mars MetNet Precursor mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide significant insights in to the Martian atmospheric behavior.The key technologies of the MetNet Lander have been qualified and the electrical qualification model (EQM) of the payload bay has been built and successfully tested.Full Qualification Model (QM) of the MetNet landing unit with the Precursor Mission payload is currently under functional tests. In the near future the QM unit will be exposed to environmental tests with qualification levels including vibrations, thermal balance, thermal cycling and mechanical impact shock. One complete flight unit of the entry, descent and landing systems (EDLS) has been manufactured and tested with acceptance levels. Another flight-like EDLS has been exposed to most of the qualification tests, and hence it may be used for flight after refurbishments. Accordingly two flight-capable EDLS systems exist. The eventual goal is to create a network of atmospheric observational posts around the Martian surface. The next step in the MetNet Precursor Mission is the demonstration of the technical robustness and scientific capabilities of the MetNet type of landing vehicle. Definition of the Precursor Mission and discussions on launch opportunities are currently under way. The baseline program development funding exists for the next five years. Flight unit manufacture of the payload bay takes about 18 months, and it will be commenced after the Precursor Mission has been defined.

  9. Sequential EMT-MET induces neuronal conversion through Sox2.

    Science.gov (United States)

    He, Songwei; Chen, Jinlong; Zhang, Yixin; Zhang, Mengdan; Yang, Xiao; Li, Yuan; Sun, Hao; Lin, Lilong; Fan, Ke; Liang, Lining; Feng, Chengqian; Wang, Fuhui; Zhang, Xiao; Guo, Yiping; Pei, Duanqing; Zheng, Hui

    2017-01-01

    Direct neuronal conversion can be achieved with combinations of small-molecule compounds and growth factors. Here, by studying the first or induction phase of the neuronal conversion induced by defined 5C medium, we show that the Sox2-mediated switch from early epithelial-mesenchymal transition (EMT) to late mesenchymal-epithelial transition (MET) within a high proliferation context is essential and sufficient for the conversion from mouse embryonic fibroblasts (MEFs) to TuJ(+) cells. At the early stage, insulin and basic fibroblast growth factor (bFGF)-induced cell proliferation, early EMT, the up-regulation of Stat3 and Sox2, and the subsequent activation of neuron projection. Up-regulated Sox2 then induced MET and directed cells towards a neuronal fate at the late stage. Inhibiting either stage of this sequential EMT-MET impaired the conversion. In addition, Sox2 could replace sequential EMT-MET to induce a similar conversion within a high proliferation context, and its functions were confirmed with other neuronal conversion protocols and MEFs reprogramming. Therefore, the critical roles of the sequential EMT-MET were implicated in direct cell fate conversion in addition to reprogramming, embryonic development and cancer progression.

  10. Interactions among catechol-O-methyltransferase genotype, parenting, and sex predict children’s internalizing symptoms and inhibitory control: Evidence for differential susceptibility

    Science.gov (United States)

    SULIK, MICHAEL J.; EISENBERG, NANCY; SPINRAD, TRACY L.; LEMERY-CHALFANT, KATHRYN; SWANN, GREGORY; SILVA, KASSONDRA M.; REISER, MARK; STOVER, DARYN A.; VERRELLI, BRIAN C.

    2015-01-01

    We used sex, observed parenting quality at 18 months, and three variants of the catechol-O-methyltransferase gene (Val158Met [rs4680], intron1 [rs737865], and 3′-untranslated region [rs165599]) to predict mothers’ reports of inhibitory and attentional control (assessed at 42, 54, 72, and 84 months) and internalizing symptoms (assessed at 24, 30, 42, 48, and 54 months) in a sample of 146 children (79 male). Although the pattern for all three variants was very similar, Val158Met explained more variance in both outcomes than did intron1, the 3′-untranslated region, or a haplotype that combined all three catechol-O-methyltransferase variants. In separate models, there were significant three-way interactions among each of the variants, parenting, and sex, predicting the intercepts of inhibitory control and internalizing symptoms. Results suggested that Val158Met indexes plasticity, although this effect was moderated by sex. Parenting was positively associated with inhibitory control for methionine–methionine boys and for valine–valine/valine–methionine girls, and was negatively associated with internalizing symptoms for methionine–methionine boys. Using the “regions of significance” technique, genetic differences in inhibitory control were found for children exposed to high-quality parenting, whereas genetic differences in internalizing were found for children exposed to low-quality parenting. These findings provide evidence in support of testing for differential susceptibility across multiple outcomes. PMID:25159270

  11. An Improved Image Segmentation Algorithm Based on MET Method

    Directory of Open Access Journals (Sweden)

    Z. A. Abo-Eleneen

    2012-09-01

    Full Text Available Image segmentation is a basic component of many computer vision systems and pattern recognition. Thresholding is a simple but effective method to separate objects from the background. A commonly used method, Kittler and Illingworth's minimum error thresholding (MET, improves the image segmentation effect obviously. Its simpler and easier to implement. However, it fails in the presence of skew and heavy-tailed class-conditional distributions or if the histogram is unimodal or close to unimodal. The Fisher information (FI measure is an important concept in statistical estimation theory and information theory. Employing the FI measure, an improved threshold image segmentation algorithm FI-based extension of MET is developed. Comparing with the MET method, the improved method in general can achieve more robust performance when the data for either class is skew and heavy-tailed.

  12. Making The Most Of MET: Mass Reconstruction From Collimated Decays

    CERN Document Server

    Spannowsky, Michael

    2013-01-01

    At hadron colliders invisible particles $\\chi$ can be inferred only through observation of the transverse component of the vectorial sum of their momenta -- missing $E_T$ or MET -- preventing reconstruction of the masses of their mother particles. Here we outline situations where prior prejudice about the event kinematics allows one to make the most of MET by decomposing it into its expected sum of transverse contributions, each of which may be promoted to a full four-momentum approximating the associated $\\chi$. Such prejudice arises when all $\\chi$ in the event are expected to be light and (anti-)parallel to a visible object, due to spin-correlations, back-to-back decays or boosted decays. We focus on the last of these, with boosted semi-invisibly decaying neutralinos widely motivated in supersymmetry (in the presence of light gravitinos, singlinos, photini or pseudo-goldstini), and demonstrate our simple method's ability to reconstruct sharp mass peaks from the MET decomposition.

  13. Metáforas rígidas

    Directory of Open Access Journals (Sweden)

    González-Marín, Carmen

    1997-04-01

    Full Text Available No disponible.Las metáforas del tipo «Julieta es el sol» se interpretan normalmente como enunciados predicativos, y en consecuencia, como usos defectivos del lenguaje. Como tratamiento alternativo, analizamos el citado tipo de metáforas como enunciados que instauran una identidad entre dos objetos y no como enunciados que predican una semejanza o una defectiva pertenencia de un objeto a una clase dada. Las metáforas que responden a un esquema «a es (un b» son consideradas como parte de un enunciado que da cuenta de un estado intencional, o en otras palabras, como el alcance de un operador epistémico M, con la fuerza ilocucionaria de una declaración. Un trasfondo platónico justifica nuestra propuesta.

  14. EMT and MET as paradigms for cell fate switching

    Institute of Scientific and Technical Information of China (English)

    Jiekai Chen; Qingkai Han; Duanqing Pei

    2012-01-01

    Cell fate determination is a major unsolved problem in cell and developmental biology,The discovery of reprogramming by pluripotent factors offers a rational system to investigate the molecular mechanisms associated with cell fate decisions.The idea that reprogramming of fibroblasts starts with a mesenchymal-epithelial transition (MET) suggests that the process is perhaps a reversal of epithelial to mesenchymal transition (EMT) found frequently during early embryogenesis,As such,we believe that investigations into MET-EMT may yield detailed molecular insights into cell fate decisions,not only for the switching between epithelial and mesenchymal cells,but also other cell types.

  15. Análise de polimorfismos nos genes CYP1A1, CYP17, COMT, GSTM1, receptor de estrogênios e progesterona em mulheres com carcinoma de ovário

    OpenAIRE

    Leite,Daniela Batista

    2009-01-01

    Objectives: To evaluate the association between polymorphisms of cytochrome P450c17 (CYP17), progesterone receptor (PROGINS), gluthatione S-transferase (GSTM1), Catechol-O-methyl transferase (COMT), and cytochrome P450c1A1 CYP1A1) genes in patients with and without ovarian cancer and to analyze the eventual association of these polymorphisms with clinical and pathological variables. Methods: A total of 103 ovarian cancer patients were seen at the Oncological Surgery Outpatients Clinic, Depart...

  16. Metingen aan varkenskarkassen met classificatie-apparatuur in combinatie met lichtreflectie-metingen met de fibre optic probe = Measurements on swine carcases with carcase grading equipment together with the fibre optic probe

    NARCIS (Netherlands)

    Wal, van der P.G.; Nijeboer, H.

    1985-01-01

    Het voorkomen van de afwijkende vleeskwaliteit PSE (pale, soft, exudative = bleek, losvezelig, nat) kan met een lichtreflectiemeter aangetoond worden. Met apparatuur voor de classificatie van varkenskarkassen zijn deze metingen ook mogelijk. In dit onderzoek is de bruikbaarheid van dergelijke meters

  17. Influence of genetic variants in TPMT and COMT associated with cisplatin induced hearing loss in patients with cancer: two new cohorts and a meta-analysis reveal significant heterogeneity between cohorts.

    Directory of Open Access Journals (Sweden)

    Melanie M Hagleitner

    Full Text Available Treatment with cisplatin-containing chemotherapy regimens causes hearing loss in 40-60% of cancer patients. It has been suggested that genetic variants in the genes encoding thiopurine S-methyltransferase (TPMT and catechol O-methyltransferase (COMT can predict the development of cisplatin-induced ototoxicity and may explain interindividual variability in sensitivity to cisplatin-induced hearing loss. Two recently published studies however, sought to validate these findings and showed inconsistent results. The aim of this study was to evaluate the role of polymorphisms in the TPMT and COMT genes in cisplatin-induced ototoxicity. Therefore we investigated two independent cohorts of 110 Dutch and 38 Spanish patients with osteosarcoma and performed a meta-analysis including all previously published studies resulting in a total population of 664 patients with cancer. With this largest meta-analysis performed to date, we show that the influence of TPMT and COMT on the development of cisplatin-induced hearing loss may be less important than previously suggested.

  18. Las metáforas de comunicación como metáforas que cobran realidad

    OpenAIRE

    Meunier, Jean Pierrer; Université catholique de Louvain

    1997-01-01

    En el paisaje teórico relativo a la comunicación, la noción de metáfora parece manifestarse y producir efectos en todas las dimensiones de la comunicación que sucesivamente se dan en el campo de la investigación: la significación, la relación, la cognición. La metáfora se presenta a la vez como un concepto iluminador y un concepto apra iluminar, como un concepto capaz de esclarecer toda clase de relaciones concretas de comunicación.