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Sample records for human catechol-o-methyltransferase comt

  1. Human catechol-O-methyltransferase: Cloning and expression of the membrane-associated form

    International Nuclear Information System (INIS)

    Bertocci, B.; Miggiano, V.; Da Prada, M.; Dembic, Z.; Lahm, H.W.; Malherbe, P.

    1991-01-01

    A cDNA clone for human catechol-O-methyltransferase was isolated from a human hepatoma cell line (Hep G2) cDNA library by hybridization screening with a porcine cDNA probe. The cDNA clone was sequenced and found to have an insert of 1226 nucleotides. The deduced primary structure of hCOMT is composed of 271 amino acid residues with the predicted molecular mass of 30 kDa. At its N terminus it has a hydrophobic segment of 21 amino acid residues that may be responsible for insertion of hCOMT into the endoplasmic reticulum membrane. The primary structure of hCOMT exhibits high homology to the porcine partial cDNA sequence (93%). The deduced amino acid sequence contains two tryptic peptide sequences (T-22, T-33) found in porcine liver catechol-O-methyltransferase (CEMT). The coding region of hCOMT cDNA was placed under the control of the cytomegalovirus promoter to transfect human kidney 293 cells. The recombinant hCOMT was shown by immunoblot analysis to be mainly associated with the membrane fraction. RNA blot analysis revealed one COMT mRNA transcript of 1.4 kilobases in Hep G2 poly(A) + RNA

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

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    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.

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

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    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

  4. Catechol-O-Methyltransferase (COMT) Gene (Val158Met) and Brain-Derived Neurotropic Factor (BDNF) (Val66Met) Genes Polymorphism in Schizophrenia: A Case-Control Study

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    Saravani, Ramin; Galavi, Hamid Reza; Lotfian Sargazi, Marzieh

    2017-01-01

    Objective: Several studies have shown that some polymorphisms of genes encoding catechol-O-methyltransferase (COMT), the key enzyme in degrading dopamine, and norepinephrine and the human brain-derived neurotropic factor (BDNF), a nerve growth factor, are strong candidates for risk of schizophrenia (SCZ). In the present study, we aimed at examining the effects of COMT Val158Met (G>A) and BDNF Val66Met (G>A) polymorphisms on SCZ risk in a sample of Iranian population. Method: This case- contro...

  5. Catechol-O-methyltransferase (COMT) genotype biases neural correlates of empathy and perceived personal distress in schizophrenia.

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    Poletti, Sara; Radaelli, Daniele; Cavallaro, Roberto; Bosia, Marta; Lorenzi, Cristina; Pirovano, Adele; Smeraldi, Enrico; Benedetti, Francesco

    2013-02-01

    The catechol-O-methyltransferase (COMT) Val(108/158)Met polymorphism (rs4680) influences enzyme activity with valine (Val) allele associated with higher enzymatic activity. Several studies suggest that factors influencing dopaminergic transmission could control response to stressful situations. Empathy is an essential element of human behavior, requires the ability to adopt another person's perspective, and has been found to be dysfunctional in schizophrenia. Twenty-eight schizophrenic patients underwent functional magnetic resonance imaging performing an empathy task. Perceived empathy has been evaluated with the Interpersonal Reactivity Index. An effect of COMT on perceived distress subscale has been shown, with methionine (Met)/Met subjects reporting lower rates of stress compared with Val/Val. Moreover, imaging results showed an effect of genotype on empathy processing in the anterior cingulate with Val/Val subjects showing the lowest activation. This is the first study of the effect of rs4680 on interpersonal distress and neural correlates of empathy in schizophrenia. We found a decrease in neural responses in areas that ensure a cognitive control of emotion that is paralleled by perceived distress in interpersonal situation; this functional pattern seems to be influenced by rs4680 COMT polymorphism. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Catechol-O-methyltransferase (COMT) genotype affects cognitive control during total sleep deprivation.

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    Satterfield, Brieann C; Hinson, John M; Whitney, Paul; Schmidt, Michelle A; Wisor, Jonathan P; Van Dongen, Hans P A

    2018-02-01

    Adaptive decision making is profoundly impaired by total sleep deprivation (TSD). This suggests that TSD impacts fronto-striatal pathways involved in cognitive control, where dopamine is a key neuromodulator. In the prefrontal cortex (PFC), dopamine is catabolized by the enzyme catechol-O-methyltransferase (COMT). A functional polymorphism (Val158Met) influences COMT's enzymatic activity, resulting in markedly different levels of prefrontal dopamine. We investigated the effect of this polymorphism on adaptive decision making during TSD. Sixty-six healthy young adults participated in one of two in-laboratory studies. After a baseline day, subjects were randomized to either a TSD group (n = 32) with 38 h or 62 h of extended wakefulness or a well-rested control group (n = 34) with 10 h nighttime sleep opportunities. Subjects performed a go/no-go reversal learning (GNGr) task at well-rested baseline and again during TSD or equivalent control. During the task, subjects were required to learn stimulus-response relationships from accuracy feedback. The stimulus-response relationships were reversed halfway through the task, which required subjects to learn the new stimulus-response relationships from accuracy feedback. Performance on the GNGr task was quantified by discriminability (d') between go and no-go stimuli before and after the stimulus-response reversal. GNGr performance did not differ between COMT genotypes when subjects were well-rested. However, TSD exposed a significant vulnerability to adaptive decision making impairment in subjects with the Val allele. Our results indicate that sleep deprivation degrades cognitive control through a fronto-striatal, dopaminergic mechanism. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Crystal structures of human 108V and 108M catechol O-methyltransferase

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    Rutherford, K.; Le Trong, I.; Stenkamp, R.E.; Parson, W.W. (UWASH)

    2008-08-01

    Catechol O-methyltransferase (COMT) plays important roles in the metabolism of catecholamine neurotransmitters and catechol estrogens. The development of COMT inhibitors for use in the treatment of Parkinson's disease has been aided by crystallographic structures of the rat enzyme. However, the human and rat proteins have significantly different substrate specificities. Additionally, human COMT contains a common valine-methionine polymorphism at position 108. The methionine protein is less stable than the valine polymorph, resulting in decreased enzyme activity and protein levels in vivo. Here we describe the crystal structures of the 108V and 108M variants of the soluble form of human COMT bound with S-adenosylmethionine (SAM) and a substrate analog, 3,5-dinitrocatechol. The polymorphic residue 108 is located in the {alpha}5-{beta}3 loop, buried in a hydrophobic pocket {approx}16 {angstrom} from the SAM-binding site. The 108V and 108M structures are very similar overall [RMSD of C{sup {alpha}} atoms between two structures (C{sup {alpha}} RMSD) = 0.2 {angstrom}], and the active-site residues are superposable, in accord with the observation that SAM stabilizes 108M COMT. However, the methionine side chain is packed more tightly within the polymorphic site and, consequently, interacts more closely with residues A22 ({alpha}2) and R78 ({alpha}4) than does valine. These interactions of the larger methionine result in a 0.7-{angstrom} displacement in the backbone structure near residue 108, which propagates along {alpha}1 and {alpha}5 toward the SAM-binding site. Although the overall secondary structures of the human and rat proteins are very similar (C{sup {alpha}} RMSD = 0.4 {angstrom}), several nonconserved residues are present in the SAM-(I89M, I91M, C95Y) and catechol- (C173V, R201M, E202K) binding sites. The human protein also contains three additional solvent-exposed cysteine residues (C95, C173, C188) that may contribute to intermolecular disulfide bond

  8. COMT Val(158)Met genotype determines the direction of cognitive effects produced by catechol-O-methyltransferase inhibition.

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    Farrell, Sarah M; Tunbridge, Elizabeth M; Braeutigam, Sven; Harrison, Paul J

    2012-03-15

    Catechol-O-methyltransferase (COMT) metabolizes dopamine. The COMT Val(158)Met polymorphism influences its activity, and multiple neural correlates of this genotype on dopaminergic phenotypes, especially working memory, have been reported. COMT activity can also be regulated pharmacologically by COMT inhibitors. The inverted-U relationship between cortical dopamine signaling and working memory predicts that the effects of COMT inhibition will differ according to COMT genotype. Thirty-four COMT Met(158)Met (Met-COMT) and 33 COMT Val(158)Val (Val-COMT) men were given a single 200-mg dose of the brain-penetrant COMT inhibitor tolcapone or placebo in a randomized, double-blind, between-subjects design. They completed the N-back task of working memory and a gambling task. In the placebo group, Met-COMT subjects outperformed Val-COMT subjects on the 2- back, and they were more risk averse. Tolcapone had opposite effects in the two genotype groups: it worsened N-back performance in Met-COMT subjects but enhanced it in Val-COMT subjects. Tolcapone made Met-COMT subjects less risk averse but Val-COMT subjects more so. In both tasks, tolcapone reversed the baseline genotype differences. Depending on genotype, COMT inhibition can enhance or impair working memory and increase or decrease risky decision making. To our knowledge, the data are the clearest demonstration to date that the direction of effect of a drug can be influenced by a polymorphism in its target gene. The results support the inverted-U model of dopamine function. The findings are of translational relevance, because COMT inhibitors are used in the adjunctive treatment of Parkinson's disease and are under evaluation in schizophrenia and other disorders. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  9. No association between catechol-O-methyltransferase (COMT) genotype and attention deficit hyperactivity disorder (ADHD) in Japanese children.

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    Yatsuga, Chiho; Toyohisa, Daiki; Fujisawa, Takashi X; Nishitani, Shota; Shinohara, Kazuyuki; Matsuura, Naomi; Ikeda, Shinobu; Muramatsu, Masaaki; Hamada, Akinobu; Tomoda, Akemi

    2014-08-01

    This study ascertained the association between attention deficit/hyperactivity disorder (ADHD) in Japanese children and a polymorphism of catechol-O-methyltransferase (COMT), a dopamine-control gene. The secondary aim of the study was the evaluation of a putative association between methylphenidate (MPH) effect/adverse effects and the COMT genotype. To ascertain the distribution of the Val158Met variant of COMT, 50 children meeting ADHD inclusion criteria were compared with 32 healthy children. Clinical improvement and the occurrence of adverse effects were measured before and 3 months after MPH administration in children with ADHD, and analyzed for genotype association. Wechsler Intelligence Scale for Children-Third Edition (WISC-III), age, MPH dose were included as co-variables. The occurrence of the COMT Val/Val genotype was significantly higher in children with ADHD (χ(2)(1)=7.13, pADHD rating scale scores, after correcting for the interaction between disorder and COMT genotype. Furthermore, no significant difference in MPH effect/adverse effects was observed in association with the COMT genotype in the ADHD group. These results showed a lack of association between the COMT Val/Val genotype and ADHD in Japan. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  10. Stress-related methylation of the catechol-O-methyltransferase Val 158 allele predicts human prefrontal cognition and activity.

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    Ursini, Gianluca; Bollati, Valentina; Fazio, Leonardo; Porcelli, Annamaria; Iacovelli, Luisa; Catalani, Assia; Sinibaldi, Lorenzo; Gelao, Barbara; Romano, Raffaella; Rampino, Antonio; Taurisano, Paolo; Mancini, Marina; Di Giorgio, Annabella; Popolizio, Teresa; Baccarelli, Andrea; De Blasi, Antonio; Blasi, Giuseppe; Bertolino, Alessandro

    2011-05-04

    DNA methylation at CpG dinucleotides is associated with gene silencing, stress, and memory. The catechol-O-methyltransferase (COMT) Val(158) allele in rs4680 is associated with differential enzyme activity, stress responsivity, and prefrontal activity during working memory (WM), and it creates a CpG dinucleotide. We report that methylation of the Val(158) allele measured from peripheral blood mononuclear cells (PBMCs) of Val/Val humans is associated negatively with lifetime stress and positively with WM performance; it interacts with stress to modulate prefrontal activity during WM, such that greater stress and lower methylation are related to reduced cortical efficiency; and it is inversely related to mRNA expression and protein levels, potentially explaining the in vivo effects. Finally, methylation of COMT in prefrontal cortex and that in PBMCs of rats are correlated. The relationship of methylation of the COMT Val(158) allele with stress, gene expression, WM performance, and related brain activity suggests that stress-related methylation is associated with silencing of the gene, which partially compensates the physiological role of the high-activity Val allele in prefrontal cognition and activity. Moreover, these results demonstrate how stress-related DNA methylation of specific functional alleles impacts directly on human brain physiology beyond sequence variation.

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

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    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.

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

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    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

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

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    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

  15. Catechol-O-Methyltransferase (COMT) Gene (Val158Met) and Brain-Derived Neurotropic Factor (BDNF) (Val66Met) Genes Polymorphism in Schizophrenia: A Case-Control Study.

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    Saravani, Ramin; Galavi, Hamid Reza; Lotfian Sargazi, Marzieh

    2017-10-01

    Objective: Several studies have shown that some polymorphisms of genes encoding catechol-O-methyltransferase (COMT), the key enzyme in degrading dopamine, and norepinephrine and the human brain-derived neurotropic factor (BDNF), a nerve growth factor, are strong candidates for risk of schizophrenia (SCZ). In the present study, we aimed at examining the effects of COMT Val158Met (G>A) and BDNF Val66Met (G>A) polymorphisms on SCZ risk in a sample of Iranian population. Method: This case- control study included 92 SCZ patients and 92 healthy controls (HCs). Genotyping of both variants (COMT Val158Met (G>A) and BDNF Val66Met (G>A)) were conducted using Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR). Results: The findings revealed that the COMT Val158Met (G>A) polymorphism was not associated with the risk/protective of SCZ in all models (OR=0.630, 95%CI=0.299-1.326, P=0.224, GA vs. GG, OR=1.416, 95%CI=0.719-2.793, P=0.314, AA vs. GG, OR=1.00, 95%CI=0.56-1.79, P=1.00 GA+AA vs. GG, OR=1.667, 95%CI=0.885-3.125, P=0.11, AA vs. GG+GA, OR=1.247, 95%CI=0.825-1.885, P=0.343, A vs. G,). However, BDNF Val66Met (G>A) variant increased the risk of SCZ (OR = 2.008 95%CI = 1.008-4.00, P = 0.047, GA vs. GG, OR = 3.876 95%CI = 1.001-14.925, P = 0.049. AA vs. GG, OR = 2.272. 95%CI = 1.204-4.347, P = 0.011, GA+AA vs. GG, OR = 2.22 95%CI = 1.29-3.82. P = 0.005, A vs. G). Conclusion: The results did not support an association between COMT Val158Met (G>A) variant and risk/protective of SCZ. Moreover, it was found that BDNF Val66Met (G>A) polymorphism may increase the risk of SCZ development. Further studies and different ethnicities are recommended to confirm the findings.

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

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

    2017-01-01

    The genetic basis controlling language development remains elusive. Previous studies of the catechol-O-methyltransferase (COMT) Val158Met 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. © The Author 2016. Published by Oxford University Press.

  17. Investigating the genetic basis of theory of mind (ToM): the role of catechol-O-methyltransferase (COMT) gene polymorphisms.

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    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. The divergent impact of catechol-O-methyltransferase (COMT) Val158Met genetic polymorphisms on executive function in adolescents with discrete patterns of childhood adversity.

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    Zhang, Huihui; Li, Jie; Yang, Bei; Ji, Tao; Long, Zhouting; Xing, Qiquan; Shao, Di; Bai, Huayu; Sun, Jiwei; Cao, Fenglin

    2018-02-01

    Catechol-O-methyltransferase (COMT) Val 158 Met functional polymorphisms play a crucial role in the development of executive function (EF), but their effect may be moderated by environmental factors such as childhood adversity. The present study aimed at testing the divergent impact of the COMT Val 158 Met genotype on EF in non-clinical adolescents with discrete patterns of childhood adversity. A total of 341 participants completed the Childhood Trauma Questionnaire, the self-reported version of the Behavior Rating Inventory of Executive Function, and self-administered questionnaires on familial function. The participants' COMT Val 158 Met genotype was determined. Associations among the variables were explored using latent class analysis and general linear models. We found that Val/Val homozygotes showed significantly worse performance on behavioral shift, relative to Met allele carriers (F=5.921, p=0.015, Partial η 2 =0.018). Moreover, three typical patterns of childhood adversity, namely, low childhood adversity (23.5%), childhood neglect (59.8%), and high childhood adversity (16.7%), were found. Both childhood neglect and high childhood adversity had a negative impact on each aspect of EF and on global EF performance. Importantly, these results provided evidence for significant interaction effects, as adolescents with the Val/Val genotype showed inferior behavioral shift performance than Met carriers (F=6.647, p=0.010, Partial η 2 =0.020) in the presence of high childhood adversity. Furthermore, there were no differences between the genotypes for childhood neglect and low childhood adversity. Overall, this is the first study to show that an interaction between the COMT genotype and childhood adversity affects EF in non-clinical adolescents. These results suggest that the COMT genotype may operate as a susceptibility gene vulnerable to an adverse environment. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Interaction between catechol-O-methyltransferase (COMT) Val158Met genotype and genetic vulnerability to schizophrenia during explicit processing of aversive facial stimuli.

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    Lo Bianco, L; Blasi, G; Taurisano, P; Di Giorgio, A; Ferrante, F; Ursini, G; Fazio, L; Gelao, B; Romano, R; Papazacharias, A; Caforio, G; Sinibaldi, L; Popolizio, T; Bellantuono, C; Bertolino, A

    2013-02-01

    Emotion dysregulation is a key feature of schizophrenia, a brain disorder strongly associated with genetic risk and aberrant dopamine signalling. Dopamine is inactivated by catechol-O-methyltransferase (COMT), whose gene contains a functional polymorphism (COMT Val158Met) associated with differential activity of the enzyme and with brain physiology of emotion processing. The aim of the present study was to investigate whether genetic risk for schizophrenia and COMT Val158Met genotype interact on brain activity during implicit and explicit emotion processing. A total of 25 patients with schizophrenia, 23 healthy siblings of patients and 24 comparison subjects genotyped for COMT Val158Met underwent functional magnetic resonance imaging during implicit and explicit processing of facial stimuli with negative emotional valence. We found a main effect of diagnosis in the right amygdala, with decreased activity in patients and siblings compared with control subjects. Furthermore, a genotype × diagnosis interaction was found in the left middle frontal gyrus, such that the effect of genetic risk for schizophrenia was evident in the context of the Val/Val genotype only, i.e. the phenotype of reduced activity was present especially in Val/Val patients and siblings. Finally, a complete inversion of the COMT effect between patients and healthy subjects was found in the left striatum during explicit processing. Overall, these results suggest complex interactions between genetically determined dopamine signalling and risk for schizophrenia on brain activity in the prefrontal cortex during emotion processing. On the other hand, the effects in the striatum may represent state-related epiphenomena of the disorder itself.

  20. Genetic moderation of the effects of cannabis: catechol-O-methyltransferase (COMT) affects the impact of Δ9-tetrahydrocannabinol (THC) on working memory performance but not on the occurrence of psychotic experiences.

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    Tunbridge, Elizabeth M; Dunn, Graham; Murray, Robin M; Evans, Nicole; Lister, Rachel; Stumpenhorst, Katharina; Harrison, Paul J; Morrison, Paul D; Freeman, Daniel

    2015-11-01

    Cannabis use can induce cognitive impairments and psychotic experiences. A functional polymorphism in the catechol-O-methyltransferase (COMT) gene (Val(158)Met) appears to influence the immediate cognitive and psychotic effects of cannabis, or ∆(9)-tetrahydrocannabinol (THC), its primary psychoactive ingredient. This study investigated the moderation of the impact of experimentally administered THC by COMT. Cognitive performance and psychotic experiences were studied in participants without a psychiatric diagnosis, using a between-subjects design (THC vs. placebo). The effect of COMT Val(158)Met genotype on the cognitive and psychotic effects of THC, administered intravenously in a double-blind, placebo-controlled manner to 78 participants who were vulnerable to paranoia, was examined. The results showed interactive effects of genotype and drug group (THC or placebo) on working memory, assayed using the Digit Span Backwards task. Specifically, THC impaired performance in COMT Val/Val, but not Met, carriers. In contrast, the effect of THC on psychotic experiences, measured using the Community Assessment of Psychic Experiences (CAPE) positive dimension, was unaffected by COMT genotype. This study is the largest to date examining the impact of COMT genotype on response to experimentally administered THC, and the first using a purely non-clinical cohort. The data suggest that COMT genotype moderates the cognitive, but not the psychotic, effects of acutely administered THC. © The Author(s) 2015.

  1. Structure related effects of flavonoid aglycones on cell cycle progression of HepG2 cells: Metabolic activation of fisetin and quercetin by catechol-O-methyltransferase (COMT).

    Science.gov (United States)

    Poór, Miklós; Zrínyi, Zita; Kőszegi, Tamás

    2016-10-01

    Dietary flavonoids are abundant in the Plant Kingdom and they are extensively studied because of their manifold pharmacological activities. Recent studies highlighted that cell cycle arrest plays a key role in their antiproliferative effect in different tumor cells. However, structure-activity relationship of flavonoids is poorly characterized. In our study the influence of 18 flavonoid aglycones (as well as two metabolites) on cell cycle distribution was investigated. Since flavonoids are extensively metabolized by liver cells, HepG2 tumor cell line was applied, considering the potential metabolic activation/inactivation of flavonoids. Our major observations are the followings: (1) Among the tested compounds diosmetin, fisetin, apigenin, lutelin, and quercetin provoked spectacular extent of G2/M phase cell cycle arrest. (2) Inhibition of catechol-O-methyltransferase enzyme by entacapone decreased the antiproliferative effects of fisetin and quercetin. (3) Geraldol and isorhamnetin (3'-O-methylated metabolites of fisetin and quercetin, respectively) demonstrated significantly higher antiproliferative effect on HepG2 cells compared to the parent compounds. Based on these results, O-methylated flavonoid metabolites or their chemically modified derivatives may be suitable candidates of tumor therapy in the future. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  2. Catechol-O-methyltransferase gene methylation and substance use in adolescents : the TRAILS study

    NARCIS (Netherlands)

    van der Knaap, L. J.; Schaefer, J. M.; Franken, I. H. A.; Verhulst, F. C.; van Oort, F. V. A.; Riese, H.

    Substance use often starts in adolescence and poses a major problem for society and individual health. The dopamine system plays a role in substance use, and catechol-O-methyltransferase (COMT) is an important enzyme that degrades dopamine. The Val(108/158)Met polymorphism modulates COMT activity

  3. Catechol-O-methyltransferase gene methylation and substance use in adolescents: The TRAILS study

    NARCIS (Netherlands)

    L.J. van der Knaap (Lisette); J.M. Schäfer (Johanna); I.H.A. Franken (Ingmar); F.C. Verhulst (Frank); F.V.A. van Oort (Floor); H. Riese (Harriëtte)

    2014-01-01

    textabstractSubstance use often starts in adolescence and poses a major problem for society and individual health. The dopamine system plays a role in substance use, and catechol-O-methyltransferase (COMT) is an important enzyme that degrades dopamine. The Val108/158Met polymorphism

  4. 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

    fatigue, sleep disorders, anxiety, depression, memory loss, and dizziness. Although the physiological mechanisms that control fibromyalgia have not been precisely established, neuroendocrine, genetic or molecular factors may be involved in fibromyalgia. OBJECTIVE: The aim of the present study was to characterize serotonin receptor (5-HT2A and catecholO-methyltransferase (COMT gene polymorphisms in Brazilian patients with fibromyalgia and to evaluate the participation of these polymorphisms in the etiology of the disease. MATERIAL AND METHODS: Genomic DNA extracted from 102 blood samples (51 patients, 51 controls was used for molecular characterization of the 5-HT2A and COMT gene polymorphisms by PCR-RFLP. RESULTS: Analysis of the 5-HT2A polymorphism revealed a frequency of 25.49% C/C, 49.02% T/C and 25.49% T/T in patients, and of 17.65% C/C, 62.74% T/C and 19.61% T/T in the control group, with no differences between the two groups.Analysis of the COMT polymorphism in patients showed a frequency of 17.65% and 45.10% for genotypes H/H and L/H, respectively. In the control group the frequency was 29.42% for H/H and 60.78% for L/H, also with no differences between the two groups. However, there was a significant difference in the frequency of the L/L genotype between patients (37.25% and controls (9.8%, which permitted differentiation between the two groups. CONCLUSION: The L/L genotype was more frequent among fibromyalgia patients. Though considering a polygenic situation and environmental factors, the molecular study of the rs4680 SNP of the COMT gene may be helpful to the identification of susceptible individuals.

  5. Radioenzymatic assay of plasma adrenaline and noradrenaline: evidence for a catechol-O-methyltransferase (COMT) inhibiting factor associated with essential hypertension

    International Nuclear Information System (INIS)

    Hoffmann, J.J.M.L.; Willemsen, J.J.; Thien, Th.; Benraad, Th.J.

    1982-01-01

    During the evaluation of a modified radioenzymatic determination of plasma adrenaline and noradrenaline, it has been found that there exists a highly significant (p 0 C, but only in plasma from patients with essential hypertension. Plasma from normotensive persons exhibits a complete lack of correlation between these factors. The consequences of the hypertension-associated COMT-inhibiting factor for the assays' specifications are discussed and data are presented for comparison with a recently-described uremia-associated COMT-inhibitor (Demassieux et al, Clin Chim Acta 115, 377-391; 1981). (Auth.)

  6. [The polymorphism of catechol-O-methyltransferase (COMT) and hemochromatosis (HFE) genes in the radiocontaminated regions residents with different chromosome aberration frequency].

    Science.gov (United States)

    Ivanova, T I; Kondrashova, T V; Krikunova, L I; Smirnova, I A; Shentereva, N I; Sychenkova, N I; Rykova, E V; Zharikova, I A; Khorokhorina, V A; Riabchenko, N I; Zamulaeva, I A

    2010-01-01

    The association between polymorphisms in genes COMT, HFE that takes part in oxidative stress regulation, and chromosome aberration frequency in lymphocytes was assessed in 278 female residents of radiation polluted regions of Central Russia: Bryansk (322 kBk/m2) and Tula Districts (137Cs - 171 kBk/m2). The C187G, G845A genotyping of HFE and G1947A (H/L) of COMT was done by means of polymerase chain reaction-restriction fragment length polymorphism. Studied population was divided into 3 subgroups by level of chromosome aberrations per cell (0-2, 3-4, >5). There was shown statistically significant difference in distribution of COMTand HFE genotypes between the groups. The high frequency of chromosome aberrations (> or = 5%) was associated with homozygotes of the high activity COMT G/G and HFE CC. Heterozygotes for G1947A COMT and C187G HFE reveal negative association with the high frequency of chromosome aberrations and correspond to "resistance factors".

  7. 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.; Kjærstad, H. L.; Støttrup, M. M.

    2017-01-01

    prefrontal cortex (dlPFC) (P=.016). Exploratory whole-brain analysis revealed a bilateral decrease in working memory-related dlPFC activity in the ValVal group vs the ValMet group which was not associated with differences in working memory performance during fMRI. Outside the MRI scanner, Val carriers...... performed worse in the CANTAB Spatial Working Memory task than Met homozygotes (P≤.006), with deficits being most pronounced in Val homozygotes. CONCLUSIONS: The association between Val allelic load, dlPFC activity and WM impairment points to a putative role of aberrant PFC dopamine tonus in the cognitive......-O-methyltransferase (COMT) gene is associated with reduced prefrontal cortex dopamine and exaggerated working memory-related prefrontal activity. This functional magnetic resonance imaging (fMRI) study investigated for the first time whether the COMT Val158Met genotype modulates prefrontal activity during spatial working...

  8. Catechol-O-methyltransferase inhibition alters pain and anxiety-related volitional behaviors through activation of β-adrenergic receptors in the rat.

    Science.gov (United States)

    Kline, R H; Exposto, F G; O'Buckley, S C; Westlund, K N; Nackley, A G

    2015-04-02

    Reduced catechol-O-methyltransferase (COMT) activity resulting from genetic variation or pharmacological depletion results in enhanced pain perception in humans and nociceptive behaviors in animals. Using phasic mechanical and thermal reflex tests (e.g. von Frey, Hargreaves), recent studies show that acute COMT-dependent pain in rats is mediated by β-adrenergic receptors (βARs). In order to more closely mimic the characteristics of human chronic pain conditions associated with prolonged reductions in COMT, the present study sought to determine volitional pain-related and anxiety-like behavioral responses following sustained as well as acute COMT inhibition using an operant 10-45°C thermal place preference task and a light/dark preference test. In addition, we sought to evaluate the effects of sustained COMT inhibition on generalized body pain by measuring tactile sensory thresholds of the abdominal region. Results demonstrated that acute and sustained administration of the COMT inhibitor OR486 increased pain behavior in response to thermal heat. Further, sustained administration of OR486 increased anxiety behavior in response to bright light, as well as abdominal mechanosensation. Finally, all pain-related behaviors were blocked by the non-selective βAR antagonist propranolol. Collectively, these findings provide the first evidence that stimulation of βARs following acute or chronic COMT inhibition drives cognitive-affective behaviors associated with heightened pain that affects multiple body sites. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. Catechol-O-methyltransferase genotype modulates cancer treatment-related cognitive deficits in breast cancer survivors.

    Science.gov (United States)

    Small, Brent J; Rawson, Kerri Sharp; Walsh, Erin; Jim, Heather S L; Hughes, Tiffany F; Iser, Lindsay; Andrykowski, Michael A; Jacobsen, Paul B

    2011-04-01

    Recent attention has focused on the negative effects of chemotherapy on the cognitive performance of cancer survivors. The current study examined modification of this risk by catechol-O-methyltransferase (COMT) genotype based on evidence in adult populations that the presence of a Val allele is associated with poorer cognitive performance. Breast cancer survivors treated with radiotherapy (n = 58), and/or chemotherapy (n = 72), and 204 healthy controls (HCs) completed tests of cognitive performance and provided saliva for COMT genotyping. COMT genotype was divided into Val carriers (Val+; Val/Val, Val/Met) or COMT-Met homozygote carriers (Met; Met/Met). COMT-Val+ carriers performed more poorly on tests of attention, verbal fluency, and motor speed relative to COMT-Met homozygotes. Moreover, COMT-Val+ carriers treated with chemotherapy performed more poorly on tests of attention relative to HC group members who were also Val+ carriers. The results suggest that persons treated with chemotherapy for breast cancer who also possess the COMT-Val gene are susceptible to negative effects on their cognitive health. This research is important because it strives to understand the factors that predispose some cancer survivors to more negative quality-of-life outcomes. Copyright © 2010 American Cancer Society.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Catechol-O-methyltransferase Val 108/158 Met polymorphism and breast cancer risk: a case control study in Syria.

    Science.gov (United States)

    Lajin, Bassam; Hamzeh, Abdul Rezzak; Ghabreau, Lina; Mohamed, Ali; Al Moustafa, Ala-Eddin; Alachkar, Amal

    2013-01-01

    Catechol-O-methyltransferase (COMT) inactivates catechol estrogens by methylation and thus may play a protective role against mutations induced by estrogen metabolites. In this study we investigated the relationship between the Vall58Met polymorphism in the COMT gene and breast cancer risk in a population-based case control study in Syria. We examined 135 breast cancer patients and 107 healthy controls in North Syria to determine the association between the functional genetic Val158Met polymorphism in the COMT gene and female breast cancer risk. There was no significant overall association between the COMT genotype and individual susceptibility to breast cancer. Our data suggest that there may be no overall association between the COMT genotype and breast cancer.

  12. Catechol-O-methyltransferase Val(158)Met association with parahippocampal physiology during memory encoding in schizophrenia.

    Science.gov (United States)

    Di Giorgio, A; Caforio, G; Blasi, G; Taurisano, P; Fazio, L; Romano, R; Ursini, G; Gelao, B; Bianco, L Lo; Papazacharias, A; Sinibaldi, L; Popolizio, T; Bellomo, A; Bertolino, A

    2011-08-01

    Catechol-O-methyltransferase (COMT) Val158Met has been associated with activity of the mesial temporal lobe during episodic memory and it may weakly increase risk for schizophrenia. However, how this variant affects parahippocampal and hippocampal physiology when dopamine transmission is perturbed is unclear. The aim of the present study was to compare the effects of the COMT Val158Met genotype on parahippocampal and hippocampal physiology during encoding of recognition memory in patients with schizophrenia and in healthy subjects. Using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI), we studied 28 patients with schizophrenia and 33 healthy subjects matched for a series of sociodemographic and genetic variables while they performed a recognition memory task. We found that healthy subjects had greater parahippocampal and hippocampal activity during memory encoding compared to patients with schizophrenia. We also found different activity of the parahippocampal region between healthy subjects and patients with schizophrenia as a function of the COMT genotype, in that the predicted COMT Met allele dose effect had an opposite direction in controls and patients. Our results demonstrate a COMT Val158Met genotype by diagnosis interaction in parahippocampal activity during memory encoding and may suggest that modulation of dopamine signaling interacts with other disease-related processes in determining the phenotype of parahippocampal physiology in schizophrenia. © Cambridge University Press 2010

  13. Analysis of Oxidative Stress Status, Catalase and Catechol-O-Methyltransferase Polymorphisms in Egyptian Vitiligo Patients

    Science.gov (United States)

    Mehaney, Dina A.; Darwish, Hebatallah A.; Hegazy, Rehab A.; Nooh, Mohammed M.; Tawdy, Amira M.; Gawdat, Heba I.; El-Sawalhi, Maha M.

    2014-01-01

    Vitiligo is the most common depigmentation disorder of the skin. Oxidative stress is implicated as one of the probable events involved in vitiligo pathogenesis possibly contributing to melanocyte destruction. Evidence indicates that certain genes including those involved in oxidative stress and melanin synthesis are crucial for development of vitiligo. This study evaluates the oxidative stress status, the role of catalase (CAT) and catechol-O-Methyltransferase (COMT) gene polymorphisms in the etiology of generalized vitiligo in Egyptians. Total antioxidant capacity (TAC) and malondialdehyde (MDA) levels as well as CAT exon 9 T/C and COMT 158 G/A polymorphisms were determined in 89 patients and 90 age and sex-matched controls. Our results showed significantly lower TAC along with higher MDA levels in vitiligo patients compared with controls. Meanwhile, genotype and allele distributions of CAT and COMT polymorphisms in cases were not significantly different from those of controls. Moreover, we found no association between both polymorphisms and vitiligo susceptibility. In conclusion, the enhanced oxidative stress with the lack of association between CAT and COMT polymorphisms and susceptibility to vitiligo in our patients suggest that mutations in other genes related to the oxidative pathway might contribute to the etiology of generalized vitiligo in Egyptian population. PMID:24915010

  14. Analysis of oxidative stress status, catalase and catechol-O-methyltransferase polymorphisms in Egyptian vitiligo patients.

    Directory of Open Access Journals (Sweden)

    Dina A Mehaney

    Full Text Available Vitiligo is the most common depigmentation disorder of the skin. Oxidative stress is implicated as one of the probable events involved in vitiligo pathogenesis possibly contributing to melanocyte destruction. Evidence indicates that certain genes including those involved in oxidative stress and melanin synthesis are crucial for development of vitiligo. This study evaluates the oxidative stress status, the role of catalase (CAT and catechol-O-Methyltransferase (COMT gene polymorphisms in the etiology of generalized vitiligo in Egyptians. Total antioxidant capacity (TAC and malondialdehyde (MDA levels as well as CAT exon 9 T/C and COMT 158 G/A polymorphisms were determined in 89 patients and 90 age and sex-matched controls. Our results showed significantly lower TAC along with higher MDA levels in vitiligo patients compared with controls. Meanwhile, genotype and allele distributions of CAT and COMT polymorphisms in cases were not significantly different from those of controls. Moreover, we found no association between both polymorphisms and vitiligo susceptibility. In conclusion, the enhanced oxidative stress with the lack of association between CAT and COMT polymorphisms and susceptibility to vitiligo in our patients suggest that mutations in other genes related to the oxidative pathway might contribute to the etiology of generalized vitiligo in Egyptian population.

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

    Directory of Open Access Journals (Sweden)

    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. Effects of acute dopamine precusor depletion on immediate reward selection bias and working memory depend on catechol-O-methyltransferase genotype.

    Science.gov (United States)

    Kelm, Mary Katherine; Boettiger, Charlotte A

    2013-12-01

    Little agreement exists as to acute dopamine (DA) manipulation effects on intertemporal choice in humans. We previously found that catechol-O-methyltransferase (COMT) Val158Met genotype predicts individual differences in immediate reward selection bias among adults. Moreover, we and others have shown that the relationship between COMT genotype and immediate reward bias is inverted in adolescents. No previous pharmacology studies testing DA manipulation effects on intertemporal choice have accounted for COMT genotype, and many have included participants in the adolescent age range (18-21 years) as adults. Moreover, many studies have included female participants without strict cycle phase control, although recent evidence demonstrates that cyclic estradiol elevations interact with COMT genotype to affect DA-dependent cognition. These factors may have interacted with DA manipulations in past studies, potentially occluding detection of effects. Therefore, we predicted that, among healthy male adults (ages 22-40 years), frontal DA tone, as indexed by COMT genotype, would interact with acute changes in DA signaling to affect intertemporal choice. In a double-blind, placebo-controlled design, we decreased central DA via administration of an amino acid beverage deficient in the DA precursors, phenylalanine and tyrosine, and tested effects on immediate reward bias in a delay-discounting (DD) task and working memory (WM) in an n-back task. We found no main effect of beverage on DD or WM performance but did find significant beverage*genotype effects. These results suggest that the effect of DA manipulations on DD depends on individual differences in frontal DA tone, which may have impeded some past efforts to characterize DA's role in immediate reward bias in humans.

  17. Properties of the Membrane Binding Component of Catechol-O-methyltransferase Revealed by Atomistic Molecular Dynamics Simulations

    DEFF Research Database (Denmark)

    Orlowski, A.; St-Pierre, J. F.; Magarkar, A.

    2011-01-01

    We used atomistic simulations to study the membrane-bound form of catechol-O-methyltransferase (MB-COMT). In particular we investigated the 26-residue transmembrane a-helical segment of MB-COMT together with the 24-residue fragment that links the transmembrane component to the main protein unit...... that was not included in our model. In numerous independent simulations we observed the formation of a salt bridge between ARC 27 and GLU40. The salt bridge closed the flexible loop that formed in the linker and kept it in the vicinity of the membrane-water interface. All simulations supported this conclusion...... that the linker has a clear affinity for the interface and preferentially arranges its residues to reside next to the membrane, without a tendency to relocate into the water phase. Furthermore, an extensive analysis of databases for sequences of membrane proteins that have a single transmembrane helical segment...

  18. The role of catechol-O-methyltransferase in catechol-enhanced erythroid differentiation of K562 cells

    International Nuclear Information System (INIS)

    Suriguga,; Li, Xiao-Fei; Li, Yang; Yu, Chun-Hong; Li, Yi-Ran; Yi, Zong-Chun

    2013-01-01

    Catechol is widely used in pharmaceutical and chemical industries. Catechol is also one of phenolic metabolites of benzene in vivo. Our previous study showed that catechol improved erythroid differentiation potency of K562 cells, which was associated with decreased DNA methylation in erythroid specific genes. Catechol is a substrate for the catechol-O-methyltransferase (COMT)-mediated methylation. In the present study, the role of COMT in catechol-enhanced erythroid differentiation of K562 cells was investigated. Benzidine staining showed that exposure to catechol enhanced hemin-induced hemoglobin accumulation and induced mRNA expression of erythroid specific genes in K562 cells. Treatment with catechol caused a time- and concentration-dependent increase in guaiacol concentration in the medium of cultured K562 cells. When COMT expression was knocked down by COMT shRNA expression in K562 cells, the production of guaiacol significantly reduced, and the sensitivity of K562 cells to cytotoxicity of catechol significantly increased. Knockdown of COMT expression by COMT shRNA expression also eliminated catechol-enhanced erythroid differentiation of K562 cells. In addition, the pre-treatment with methyl donor S-adenosyl-L-methionine or its demethylated product S-adenosyl-L-homocysteine induced a significant increase in hemin-induced Hb synthesis in K562 cells and the mRNA expression of erythroid specific genes. These findings indicated that O-methylation catalyzed by COMT acted as detoxication of catechol and involved in catechol-enhanced erythroid differentiation of K562 cells, and the production of S-adenosyl-L-homocysteine partly explained catechol-enhanced erythroid differentiation. - Highlights: • Catechol enhanced hemin-induced hemoglobin accumulation. • COMT-catalyzed methylation acted as detoxication of catechol. • COMT involved in catechol-enhanced erythroid differentiation

  19. The role of catechol-O-methyltransferase in catechol-enhanced erythroid differentiation of K562 cells

    Energy Technology Data Exchange (ETDEWEB)

    Suriguga,; Li, Xiao-Fei; Li, Yang; Yu, Chun-Hong; Li, Yi-Ran; Yi, Zong-Chun, E-mail: yizc@buaa.edu.cn

    2013-12-15

    Catechol is widely used in pharmaceutical and chemical industries. Catechol is also one of phenolic metabolites of benzene in vivo. Our previous study showed that catechol improved erythroid differentiation potency of K562 cells, which was associated with decreased DNA methylation in erythroid specific genes. Catechol is a substrate for the catechol-O-methyltransferase (COMT)-mediated methylation. In the present study, the role of COMT in catechol-enhanced erythroid differentiation of K562 cells was investigated. Benzidine staining showed that exposure to catechol enhanced hemin-induced hemoglobin accumulation and induced mRNA expression of erythroid specific genes in K562 cells. Treatment with catechol caused a time- and concentration-dependent increase in guaiacol concentration in the medium of cultured K562 cells. When COMT expression was knocked down by COMT shRNA expression in K562 cells, the production of guaiacol significantly reduced, and the sensitivity of K562 cells to cytotoxicity of catechol significantly increased. Knockdown of COMT expression by COMT shRNA expression also eliminated catechol-enhanced erythroid differentiation of K562 cells. In addition, the pre-treatment with methyl donor S-adenosyl-L-methionine or its demethylated product S-adenosyl-L-homocysteine induced a significant increase in hemin-induced Hb synthesis in K562 cells and the mRNA expression of erythroid specific genes. These findings indicated that O-methylation catalyzed by COMT acted as detoxication of catechol and involved in catechol-enhanced erythroid differentiation of K562 cells, and the production of S-adenosyl-L-homocysteine partly explained catechol-enhanced erythroid differentiation. - Highlights: • Catechol enhanced hemin-induced hemoglobin accumulation. • COMT-catalyzed methylation acted as detoxication of catechol. • COMT involved in catechol-enhanced erythroid differentiation.

  20. 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; Drury, Stacy S

    2014-10-01

    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. 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]). 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. 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.

  1. Catechol-o-methyltransferase gene polymorphism modifies the effect of coffee intake on incidence of acute coronary events.

    Directory of Open Access Journals (Sweden)

    Pertti Happonen

    Full Text Available BACKGROUND: The role of coffee intake as a risk factor for coronary heart disease (CHD has been debated for decades. We examined whether the relationship between coffee intake and incidence of CHD events is dependent on the metabolism of circulating catecholamines, as determined by functional polymorphism of the catechol-O-methyltransferase (COMT gene. METHODOLOGY/PRINCIPAL FINDINGS: In a cohort of 773 men who were 42 to 60 years old and free of symptomatic CHD at baseline in 1984-89, 78 participants experienced an acute coronary event during an average follow-up of 13 years. In logistic regression adjusting for age, smoking, family history of CHD, vitamin C deficiency, blood pressure, plasma cholesterol concentration, and diabetes, the odds ratio (90% confidence interval comparing heavy coffee drinkers with the low activity COMT genotype with those with the high activity or heterozygotic genotypes was 3.2 (1.2-8.4. Urinary adrenaline excretion increased with increasing coffee intake, being over two-fold in heavy drinkers compared with nondrinkers (p = 0.008 for trend. CONCLUSIONS/SIGNIFICANCE: Heavy coffee consumption increases the incidence of acute coronary events in men with low but not high COMT activity. Further studies are required to determine to which extent circulating catecholamines mediate the relationship between coffee intake and CHD.

  2. The role of catechol-O-methyltransferase in catechol-enhanced erythroid differentiation of K562 cells.

    Science.gov (United States)

    Suriguga; Li, Xiao-Fei; Li, Yang; Yu, Chun-Hong; Li, Yi-Ran; Yi, Zong-Chun

    2013-12-15

    Catechol is widely used in pharmaceutical and chemical industries. Catechol is also one of phenolic metabolites of benzene in vivo. Our previous study showed that catechol improved erythroid differentiation potency of K562 cells, which was associated with decreased DNA methylation in erythroid specific genes. Catechol is a substrate for the catechol-O-methyltransferase (COMT)-mediated methylation. In the present study, the role of COMT in catechol-enhanced erythroid differentiation of K562 cells was investigated. Benzidine staining showed that exposure to catechol enhanced hemin-induced hemoglobin accumulation and induced mRNA expression of erythroid specific genes in K562 cells. Treatment with catechol caused a time- and concentration-dependent increase in guaiacol concentration in the medium of cultured K562 cells. When COMT expression was knocked down by COMT shRNA expression in K562 cells, the production of guaiacol significantly reduced, and the sensitivity of K562 cells to cytotoxicity of catechol significantly increased. Knockdown of COMT expression by COMT shRNA expression also eliminated catechol-enhanced erythroid differentiation of K562 cells. In addition, the pre-treatment with methyl donor S-adenosyl-L-methionine or its demethylated product S-adenosyl-L-homocysteine induced a significant increase in hemin-induced Hb synthesis in K562 cells and the mRNA expression of erythroid specific genes. These findings indicated that O-methylation catalyzed by COMT acted as detoxication of catechol and involved in catechol-enhanced erythroid differentiation of K562 cells, and the production of S-adenosyl-L-homocysteine partly explained catechol-enhanced erythroid differentiation. © 2013.

  3. 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.

  4. 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.

  5. 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.

  6. Association of codon 108/158 catechol-O-methyltransferase gene polymorphism with the psychiatric manifestations of velo-cardio-facial syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Lachman, H.M.; Papolos, D.F.; Veit, S. [Albert Einstein College of Medicine, Bronx, NY (United States)] [and others

    1996-09-20

    Velo-cardio-facial-syndrome (VCFS) is a common congenital disorder associated with typical facial appearance, cleft palate, cardiac defects, and learning disabilities. The majority of patients have an interstitial deletion on chromosome 22q11. In addition to physical abnormalities, a variety of psychiatric illnesses have been reported in patients with VCFS, including schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder. The psychiatric manifestations of VCFS could be due to haploinsufficiency of a gene(s) within 22q11. One candidate that has been mapped to this region is catechol-O-methyltransferase (COMT). We recently identified a polymorphism in the COMT gene that leads to a valine{r_arrow}methionine substitution at amino acid 158 of the membrane-bound form of the enzyme. Homozygosity for COMT158{sup met} leads to a 3- to 4-fold reduction in enzymatic activity, compared with homozygotes for COMT158{sup met}. We now report that in a population of patients with VCFS, there is an apparent association between the low-activity allele, COMT158{sup met}, and the development of bipolar spectrum disorder, and in particular, a rapid-cycling form. 33 refs., 3 tabs.

  7. [Effect of Electroacupuncture on Expression of Catechol-O-methyltransferase in the Inferior Colliculus and Auditory Cortex in Age-related Hearing Loss Guinea Pigs].

    Science.gov (United States)

    Liu, Shu-Yun; Deng, Li-Qiang; Yang, Ye; Yin, Ze-Deng

    2017-04-25

    To observe the expression of catechol-O-methyltransferase (COMT) in inferior colliculus and auditory cortex of guinea pigs with age-related hearing loss(AHL) induced by D-galactose, so as to explore the possible mechanism of electroacupuncture(EA) underlying preventing AHL. Thirty 3-month-old guinea pigs were randomly divided into control group, model group and EA group( n =10 in each group), and ten 18-month-old guinea pigs were allocated as elderly group. The AHL model was established by subcutaneous injection of D-galactose. EA was applied to bilateral "Yifeng"(SJ 17) and "Tinggong"(SI 19) for 15 min in the EA group while modeling, once daily for 6 weeks. After treatment, the latency of auditory brainstem response(ABR) Ⅲ wave was measured by a brain-stem evoked potentiometer. The expressions of COMT in the inferior colliculus and auditory cortex were detected by Western blot. Compared with the control group, the latencies of ABR Ⅲ wave were significantly prolonged and the expressions of COMT in the inferior colliculus and auditory cortex were significantly decreased in the model group and the elderly group( P guinea pigs, which may contribute to its effect in up-regulating the expression of COMT in the inferior colliculus and auditory cortex.

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

    Directory of Open Access Journals (Sweden)

    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. Catechol-O-methyltransferase gene variants may associate with negative symptom response and plasma concentrations of prolactin in schizophrenia after amisulpride treatment.

    Science.gov (United States)

    Chen, Chun-Yen; Yeh, Yi-Wei; Kuo, Shin-Chang; Ho, Pei-Shen; Liang, Chih-Sung; Yen, Che-Hung; Lu, Ru-Band; Huang, San-Yuan

    2016-03-01

    Catechol-O-methyltransferase (COMT) enzyme is involved in the pathogenesis of psychotic symptoms and may be associated with a therapeutic response to antipsychotic drugs. The aim of this study was to examine the relationship between COMT variants, plasma prolactin level, and the therapeutic effectiveness of amisulpride treatment in patients with schizophrenia. A 12-week naturalistic study of amisulpride treatment was carried out in 185 Han Chinese patients with schizophrenia. The patients were screened for 14 single-nucleotide polymorphisms of the COMT gene. The Positive and Negative Syndrome Scale (PANSS) was used to assess the improvement of psychopathological symptoms from the baseline to the end point in each subject. For better presentation of time-course changes in response status, a mixed model for repeated-measures (MMRM) analysis of symptom improvement during the 12-week treatment period was conducted. The change in plasma prolactin level after amisulpride treatment was also examined (n=51). No significant differences in the genotype frequencies of the COMT variants investigated were observed between responders and non-responders. Moreover, an MMRM analysis of psychopathological symptom improvement during the 12-week treatment course showed that it depended significantly on COMT variants (rs4680, rs4633, and rs6267), particularly regarding changes in negative symptoms. The increase in plasma prolactin levels observed was influenced by the COMT rs4680 variant and was positively correlated with a reduction in PANSS negative scores. Our results suggest that variation of the COMT gene is associated with treatment response regarding negative symptoms and prolactin changes after amisulpride treatment in patients with schizophrenia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. 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

  11. Genotype distribution of estrogen receptor-alpha, catechol-O-methyltransferase, and cytochrome P450 17 gene polymorphisms in Caucasian women with uterine leiomyomas.

    Science.gov (United States)

    Denschlag, Dominik; Bentz, Eva-Katrin; Hefler, Lukas; Pietrowski, Detlef; Zeillinger, Robert; Tempfer, Clemens; Tong, Dan

    2006-02-01

    To evaluate the association between the presence of uterine leiomyomas and three functional single nucleotide polymorphisms (SNPs) of the estrogen receptor alpha (ESR1), catechol-O-methyltransferase (COMT), and cytochrom P450 17 (CYP17A) genes, which have been described to modify the estrogen metabolism. Prospective case control study. Academic research institution. One hundred thirty women with clinically and surgically diagnosed uterine leiomyomas and 139 population controls. Peripheral venous puncture. Polymerase chain reaction and pyrosequencing were performed to genotype women with respect to the ESR1 IVS1-397 T/C (PvuII), COMT G158A, and the CYP17A 34T-->C SNPs. Comparing women with uterine leiomyomas and controls, no statistically significant differences with respect to allele frequency and genotype distribution were ascertained for ESR1 IVS 1-397 T/C (PvuII) (P=0.9 and P=0.6, respectively), COMT G158A (P=0.3 and P=0.6, respectively), and CYP17A 34T-->C (P=0.1 and P=0.5, respectively). When all two-way interactions of investigated SNPs were ascertained, no significant interactions were observed. In a multivariate model, no SNP was significantly associated with leiomyomas. Carriage of the ESR1 IVS1-397 T/C (PvuII), COMT G158A, and the CYP17A 34T-->C SNPs is not associated with the susceptibility to uterine leiomyoma in a Caucasian population.

  12. Catechol-O-Methyltransferase Genotypes and Parenting Influence on Long-Term Executive Functioning After Moderate to Severe Early Childhood Traumatic Brain Injury: An Exploratory Study.

    Science.gov (United States)

    Kurowski, Brad G; Treble-Barna, Amery; Zang, Huaiyu; Zhang, Nanhua; Martin, Lisa J; Yeates, Keith Owen; Taylor, H Gerry; Wade, Shari L

    To examine catechol-O-methyltransferase (COMT) rs4680 genotypes as moderators of the effects of parenting style on postinjury changes in parent behavior ratings of executive dysfunction following moderate to severe early childhood traumatic brain injury. Research was conducted in an outpatient setting. Participants included children admitted to hospital with moderate to severe traumatic brain injury (n = 55) or orthopedic injuries (n = 70) between ages 3 and 7 years. Prospective cohort followed over 7 years postinjury. Parenting Practices Questionnaire and the Behavior Rating Inventory of Executive Functioning obtained at baseline, 6, 12, and 18 months, and 3.5 and 6.8 years postinjury. DNA was collected from saliva samples, purified using the Oragene (DNA Genotek, Ottawa, Ontario, Canada) OG-500 self-collection tubes, and analyzed using TaqMan (Applied Biosystems, Thermo Fisher Scientific, Waltham, Massachusetts) assay protocols to identify the COMT rs4680 polymorphism. Linear mixed models revealed a significant genotype × parenting style × time interaction (F = 5.72, P = .02), which suggested that the adverse effects of authoritarian parenting on postinjury development of executive functioning were buffered by the presence of the COMT AA genotype (lower enzyme activity, higher dopamine levels). There were no significant associations of executive functioning with the interaction between genotype and authoritative or permissive parenting ratings. The lower activity COMT rs4680 genotype may buffer the negative effect of authoritarian parenting on long-term executive functioning following injury in early childhood. The findings provide preliminary evidence for associations of parenting style with executive dysfunction in children and for a complex interplay of genetic and environmental factors as contributors to decreases in these problems after traumatic injuries in children. Further investigation is warranted to understand the interplay among genetic and

  13. Determination of catechol O-methyltransferase activity in relation to melanin metabolism using high-performance liquid chromatography with fluorimetric detection

    NARCIS (Netherlands)

    Smit, N. P.; Pavel, S.; Kammeyer, A.; Westerhof, W.

    1990-01-01

    A new sensitive method for the determination of catechol O-methyltransferase activity has been developed. The method is based on the O-methylation of the indolic intermediates of melanin metabolism. The substrate, 5,6-dihydroxyindole-2-carboxylic acid, is converted by the enzyme to two O-methylated

  14. Genetic variation in COMT and PRODH is associated with brain anatomy in patients with schizophrenia

    NARCIS (Netherlands)

    Zinkstok, J.; Schmitz, N.; van Amelsvoort, T.; Moeton, M.; Baas, F.; Linszen, D.

    2008-01-01

    Haploinsufficiency of 22q11 genes including catechol-O-methyltransferase (COMT) and proline dehydrogenase (PRODH) may result in structural and functional brain abnormalities and increased vulnerability to schizophrenia as observed in patients with microdeletions of 22q11. Thus, COMT and PRODH could

  15. 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.

  16. A potyvirus-based gene vector allows producing active human S-COMT and animal GFP, but not human sorcin, in vector-infected plants.

    Science.gov (United States)

    Kelloniemi, Jani; Mäkinen, Kristiina; Valkonen, Jari P T

    2006-05-01

    Potato virus A (PVA), a potyvirus with a (+)ssRNA genome translated to a large polyprotein, was engineered and used as a gene vector for expression of heterologous proteins in plants. Foreign genes including jellyfish GFP (Aequorea victoria) encoding the green fluorescent protein (GFP, 27 kDa) and the genes of human origin (Homo sapiens) encoding a soluble resistance-related calcium-binding protein (sorcin, 22 kDa) and the catechol-O-methyltransferase (S-COMT; 25 kDa) were cloned between the cistrons for the viral replicase and coat protein (CP). The inserts caused no adverse effects on viral infectivity and virulence, and the inserted sequences remained intact in progeny viruses in the systemically infected leaves. The heterologous proteins were released from the viral polyprotein following cleavage by the main viral proteinase, NIa, at engineered proteolytic processing sites flanking the insert. Active GFP, as indicated by green fluorescence, and S-COMT with high levels of enzymatic activity were produced. In contrast, no sorcin was detected despite the expected equimolar amounts of the foreign and viral proteins being expressed as a polyprotein. These data reveal inherent differences between heterologous proteins in their suitability for production in plants.

  17. 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

  18. The COMT val158met polymorphism and brain morphometry in healthy young adults

    NARCIS (Netherlands)

    Zinkstok, Janneke; Schmitz, Nicole; van Amelsvoort, Therese; de Win, Maartje; van den Brink, Wim; Baas, Frank; Linszen, Don

    2006-01-01

    Catechol-O-methyltransferase (COMT) is the most important mechanism for dopamine degradation in the prefrontal cortex and contains a functional polymorphism (val(158)met) influencing enzyme activity. The low-activity met allele has been associated with better performance on cognitive tasks relying

  19. COMT Val158Met genotype as a risk factor for problem behaviors in youth

    NARCIS (Netherlands)

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

    2010-01-01

    textabstractObjective: 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

  20. Remote memories are enhanced by COMT activity through dysregulation of the endocannabinoid system in the prefrontal cortex.

    Science.gov (United States)

    Scheggia, D; Zamberletti, E; Realini, N; Mereu, M; Contarini, G; Ferretti, V; Managò, F; Margiani, G; Brunoro, R; Rubino, T; De Luca, M A; Piomelli, D; Parolaro, D; Papaleo, F

    2018-04-01

    The prefrontal cortex (PFC) is a crucial hub for the flexible modulation of recent memories (executive functions) as well as for the stable organization of remote memories. Dopamine in the PFC is implicated in both these processes and genetic variants affecting its neurotransmission might control the unique balance between cognitive stability and flexibility present in each individual. Functional genetic variants in the catechol-O-methyltransferase (COMT) gene result in a different catabolism of dopamine in the PFC. However, despite the established role played by COMT genetic variation in executive functions, its impact on remote memory formation and recall is still poorly explored. Here we report that transgenic mice overexpressing the human COMT-Val gene (COMT-Val-tg) present exaggerated remote memories (>50 days) while having unaltered recent memories (remote memories as silencing COMT Val overexpression starting from 30 days after the initial aversive conditioning normalized remote memories. COMT genetic overactivity produced a selective overdrive of the endocannabinoid system within the PFC, but not in the striatum and hippocampus, which was associated with enhanced remote memories. Indeed, acute pharmacological blockade of CB1 receptors was sufficient to rescue the altered remote memory recall in COMT-Val-tg mice and increased PFC dopamine levels. These results demonstrate that COMT genetic variations modulate the retrieval of remote memories through the dysregulation of the endocannabinoid system in the PFC.

  1. Modification of Depression by COMT val[superscript 158]Met Polymorphism in Children Exposed to Early Severe Psychosocial Deprivation

    Science.gov (United States)

    Drury, Stacy S.; Theall, Katherine P.; Smyke, Anna T.; Keats, Bronya J. B.; Egger, Helen L.; Nelson, Charles A.; Fox, Nathan A.; Marshall, Peter J.; Zeanah, Charles H.

    2010-01-01

    Objective: To examine the impact of the catechol-O-methyltransferase (COMT) val[superscript 158]met allele on depressive symptoms in young children exposed to early severe social deprivation as a result of being raised in institutions. Methods: One hundred thirty six children from the Bucharest Early Intervention Project (BEIP) were randomized…

  2. Determination of free and conjugated catecholamines and L-3,4-dihydroxyphenylalanine in plasma and urine: evidence for a catechol-O-methyltransferase inhibitor in uraemia

    International Nuclear Information System (INIS)

    Demassieux, S.; Corneille, L.; Lachance, S.; Carriere, S.

    1981-01-01

    A sensitive, accurate and reproducible method has been developed for the determination of free and conjugated catecholamines and L-3,4-dihydroxyphenylalanine in plasma and urine. The assay involves the enzymatic conversion of these compounds to their radio-labelled O-methylated derivatives using catechol-O-methyltransferase and S-adenosyl-L-[methyl- 3 H]methionine. Recoveries of 75 +- 5% for dopamine, 70 +- 5% for adrenaline and 65 +- 5% for noradrenaline were obtained. The sensitivities were 0.5 pg for adrenaline and noradrenaline and 5-7 pg for dopamine and dihydroxyphenylalanine. Measurements of conjugated catecholamines were performed after mild acid hydrolysis for 20 min at 95 0 C. During this procedure no degradation of the catecholamines was observed. This assay led to the discovery of a dialyzable factor in the plasma of chronic uraemic patients which inhibits catechol-O-methyltransferase activity in vitro. The mean 22% inhibition observed for unhydrolyzed plasma increased to 42% after hydrolysis. The identity of this inhibitor which exists as an inactive conjugated form, probably a sulphate ester, and its implication in physiopathological disorders remain to be established. (Auth.)

  3. 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

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

    Science.gov (United States)

    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 (PScale 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.

  5. COMT genotype, gambling activity, and cognition

    DEFF Research Database (Denmark)

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

    2015-01-01

    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......Neuropsychological studies of adults with problem gambling indicate impairments across multiple cognitive domains. Catechol-O-methyltransferase (COMT) plays a unique role in the regulation of dopamine in the prefrontal cortex, and has been implicated in the cognitive dysfunction evident in problem...... 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...

  6. The dual-state theory of prefrontal cortex dopamine function with relevance to catechol-o-methyltransferase genotypes and schizophrenia.

    Science.gov (United States)

    Durstewitz, Daniel; Seamans, Jeremy K

    2008-11-01

    There is now general consensus that at least some of the cognitive deficits in schizophrenia are related to dysfunctions in the prefrontal cortex (PFC) dopamine (DA) system. At the cellular and synaptic level, the effects of DA in PFC via D1- and D2-class receptors are highly complex, often apparently opposing, and hence difficult to understand with regard to their functional implications. Biophysically realistic computational models have provided valuable insights into how the effects of DA on PFC neurons and synaptic currents as measured in vitro link up to the neural network and cognitive levels. They suggest the existence of two discrete dynamical regimes, a D1-dominated state characterized by a high energy barrier among different network patterns that favors robust online maintenance of information and a D2-dominated state characterized by a low energy barrier that is beneficial for flexible and fast switching among representational states. These predictions are consistent with a variety of electrophysiological, neuroimaging, and behavioral results in humans and nonhuman species. Moreover, these biophysically based models predict that imbalanced D1:D2 receptor activation causing extremely low or extremely high energy barriers among activity states could lead to the emergence of cognitive, positive, and negative symptoms observed in schizophrenia. Thus, combined experimental and computational approaches hold the promise of allowing a detailed mechanistic understanding of how DA alters information processing in normal and pathological conditions, thereby potentially providing new routes for the development of pharmacological treatments for schizophrenia.

  7. Allelic variation of the COMT gene in a despotic primate society: A haplotype is related to cortisol excretion in Macaca fuscata.

    Science.gov (United States)

    Pflüger, Lena S; Gutleb, Daria R; Hofer, Martin; Fieder, Martin; Wallner, Bernard; Steinborn, Ralf

    2016-02-01

    Sequence variations in genes of the monoamine neurotransmitter system and their common function in human and non-human primate species are an ongoing issue of investigation. However, the COMT gene, coding for the catechol-O-methyltransferase, has not yet attracted much scientific attention regarding its functional role in non-human primates. Considering that a polymorphism of the human COMT gene affects the enzyme activity and cortisol level in response to a social stressor, this study investigated the impact of COMT on endocrine stress and behavioural parameters in Japanese macaques (Macaca fuscata). The species exemplifies a despotic hierarchy in which males' social rank positions require an adaptation of behaviour strategies. During the mating period steroid secretion and the frequency of aggressive encounters between males increase. We addressed i) whether this species exhibits potential functional COMT variants, ii) whether these variants are associated with faecal cortisol excretion of males, iii) how they are distributed among different social rank positions and iv) whether they are associated with behavioural strategies during times of mate competition. By genotyping 26 males we identified three COMT haplotypes (HT), including a putative splice mutant (HT3). This variant was associated with increased cortisol excretion. Given the observed inverse correlation between cortisol and physical aggression, we assume that different COMT haplotypes may predispose individuals to pursue more or less aggressive strategies. How these gene-stress effects might favour a specific social role is discussed. Our study of non-invasive genotyping in combination with behavioural and endocrine parameters represents an important step towards the understanding of gene-stress effects in a hierarchically organised primate society. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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    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.

  9. 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

  10. Association between Gene Polymorphisms and Pain Sensitivity Assessed in a Multi-Modal Multi-Tissue Human Experimental Model - An Explorative Study

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    Nielsen, Lecia Møller; Olesen, Anne Estrup; Sato, Hiroe

    2016-01-01

    The genetic influence on sensitivity to noxious stimuli (pain sensitivity) remains controversial and needs further investigation. In the present study, the possible influence of polymorphisms in three opioid receptor (OPRM, OPRD and OPRK) genes and the catechol-O-methyltransferase (COMT) gene...... on pain sensitivity in healthy participants was investigated. Catechol-O-methyltransferase has an indirect effect on the mu opioid receptor by changing its activity through an altered endogenous ligand effect. Blood samples for genetic analysis were withdrawn in a multi-modal and multi-tissue experimental......, electrical and thermal visceral stimulations. A cold pressor test was also conducted. DNA was available from 38 of 40 participants. Compared to non-carriers of the COMT rs4680A allele, carriers reported higher bone pressure pain tolerance threshold (i.e. less pain) by up to 23.8% (p

  11. Epistasis between dopamine regulating genes identifies a nonlinear response of the human hippocampus during memory tasks.

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    Bertolino, Alessandro; Di Giorgio, Annabella; Blasi, Giuseppe; Sambataro, Fabio; Caforio, Grazia; Sinibaldi, Lorenzo; Latorre, Valeria; Rampino, Antonio; Taurisano, Paolo; Fazio, Leonardo; Romano, Raffaella; Douzgou, Sofia; Popolizio, Teresa; Kolachana, Bhaskar; Nardini, Marcello; Weinberger, Daniel R; Dallapiccola, Bruno

    2008-08-01

    Dopamine modulation of neuronal activity in prefrontal cortex maps to an inverted U-curve. Dopamine is also an important factor in regulation of hippocampal mediated memory processing. Here, we investigated the effect of genetic variation of dopamine inactivation via catechol-O-methyltransferase (COMT) and the dopamine transporter (DAT) on hippocampal activity in healthy humans during different memory conditions. Using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in 82 subjects matched for a series of demographic and genetic variables, we studied the effect of the COMT valine (Val)(158)methionine (Met) and the DAT 3' variable number tandem repeat (VNTR) polymorphisms on function of the hippocampus during encoding of recognition memory and during working memory. Our results consistently demonstrated a double dissociation so that DAT 9-repeat carrier alleles modulated activity in the hippocampus in the exact opposite direction of DAT 10/10-repeat alleles based on COMT Val(158)Met genotype during different memory conditions. Similar results were evident in ventrolateral and dorsolateral prefrontal cortex. These findings suggest that genetically determined dopamine signaling during memory processing maps to a nonlinear relationship also in the hippocampus. Our data also demonstrate in human brain epistasis of two genes implicated in dopamine signaling on brain activity during different memory conditions.

  12. 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.

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

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    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.

  14. 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.

  15. COMT ValMet moderation of cannabis-induced psychosis: a momentary assessment study of 'switching on' hallucinations in the flow of daily life.

    Science.gov (United States)

    Henquet, C; Rosa, A; Delespaul, P; Papiol, S; Fananás, L; van Os, J; Myin-Germeys, I

    2009-02-01

    A functional polymorphism in the catechol-o-methyltransferase gene (COMT Val(158)Met) may moderate the psychosis-inducing effects of cannabis. In order to extend this finding to dynamic effects in the flow of daily life, a momentary assessment study of psychotic symptoms in response to cannabis use was conducted. The experience sampling technique was used to collect data on cannabis use and occurrence of symptoms in daily life in patients with a psychotic disorder (n = 31) and healthy controls (n = 25). Carriers of the COMT Val(158)Met Val allele, but not subjects with the Met/Met genotype, showed an increase in hallucinations after cannabis exposure, conditional on prior evidence of psychometric psychosis liability. The findings confirm that in people with psychometric evidence of psychosis liability, COMT Val(158)Met genotype moderates the association between cannabis and psychotic phenomena in the flow of daily life.

  16. 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.

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

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

    2018-04-01

    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.

  18. Physical and verbal aggressive behavior and COMT genotype: Sensitivity to the environment.

    Science.gov (United States)

    Tuvblad, Catherine; Narusyte, Jurgita; Comasco, Erika; Andershed, Henrik; Andershed, Anna-Karin; Colins, Olivier F; Fanti, Kostas A; Nilsson, Kent W

    2016-07-01

    Catechol-O-methyltransferase (COMT) genotype has been implicated as a vulnerability factor for several psychiatric diseases as well as aggressive behavior, either directly, or in interaction with an adverse environment. The present study aimed at investigating the susceptibility properties of COMT genotype to adverse and favorable environment in relation to physical and verbal aggressive behavior. The COMT Val158Met polymorphism was genotyped in a Swedish population-based cohort including 1,783 individuals, ages 20-24 years (47% males). A significant three-way interaction was found, after correction for multiple testing, between COMT genotype, exposure to violence, and parent-child relationship in association with physical but not verbal aggressive behavior. Homozygous for the Val allele reported lower levels of physical aggressive behavior when they were exposed to violence and at the same time experienced a positive parent-child relationship compared to Met carriers. Thus, susceptibility properties of COMT genotype were observed in relation to physical aggressive behavior supporting the hypothesis that COMT genotypes are modifying the sensitivity to environment that confers either risk or protection for aggressive behavior. As these are novel findings, they warrant further investigation and replication in independent samples. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. Interaction Effects of BDNF and COMT Genes on Resting-State Brain Activity and Working Memory

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    Chen, Wen; Chen, Chunhui; Xia, Mingrui; Wu, Karen; Chen, Chuansheng; He, Qinghua; Xue, Gui; Wang, Wenjing; He, Yong; Dong, Qi

    2016-01-01

    Catechol-O-methyltransferase (COMT) and brain-derived neurotrophic factor (BDNF) genes have been found to interactively influence working memory (WM) as well as brain activation during WM tasks. However, whether the two genes have interactive effects on resting-state activities of the brain and whether these spontaneous activations correlate with WM are still unknown. This study included behavioral data from WM tasks and genetic data (COMT rs4680 and BDNF Val66Met) from 417 healthy Chinese adults and resting-state fMRI data from 298 of them. Significant interactive effects of BDNF and COMT were found for WM performance as well as for resting-state regional homogeneity (ReHo) in WM-related brain areas, including the left medial frontal gyrus (lMeFG), left superior frontal gyrus (lSFG), right superior and medial frontal gyrus (rSMFG), right medial orbitofrontal gyrus (rMOFG), right middle frontal gyrus (rMFG), precuneus, bilateral superior temporal gyrus, left superior occipital gyrus, right middle occipital gyrus, and right inferior parietal lobule. Simple effects analyses showed that compared to other genotypes, subjects with COMT-VV/BDNF-VV had higher WM and lower ReHo in all five frontal brain areas. The results supported the hypothesis that COMT and BDNF polymorphisms influence WM performance and spontaneous brain activity (i.e., ReHo). PMID:27853425

  20. The effects of gender and COMT Val158Met polymorphism on fearful facial affect recognition: a fMRI study.

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    Kempton, Matthew J; Haldane, Morgan; Jogia, Jigar; Christodoulou, Tessa; Powell, John; Collier, David; Williams, Steven C R; Frangou, Sophia

    2009-04-01

    The functional catechol-O-methyltransferase (COMT Val108/158Met) polymorphism has been shown to have an impact on tasks of executive function, memory and attention and recently, tasks with an affective component. As oestrogen reduces COMT activity, we focused on the interaction between gender and COMT genotype on brain activations during an affective processing task. We used functional MRI (fMRI) to record brain activations from 74 healthy subjects who engaged in a facial affect recognition task; subjects viewed and identified fearful compared to neutral faces. There was no main effect of the COMT polymorphism, gender or genotypexgender interaction on task performance. We found a significant effect of gender on brain activations in the left amygdala and right temporal pole, where females demonstrated increased activations over males. Within these regions, Val/Val carriers showed greater signal magnitude compared to Met/Met carriers, particularly in females. The COMT Val108/158Met polymorphism impacts on gender-related patterns of activation in limbic and paralimbic regions but the functional significance of any oestrogen-related COMT inhibition appears modest.

  1. COMT Val(108/158)Met polymorphism effects on emotional brain function and negativity bias.

    Science.gov (United States)

    Williams, Leanne M; Gatt, Justine M; Grieve, Stuart M; Dobson-Stone, Carol; Paul, Robert H; Gordon, Evian; Schofield, Peter R

    2010-11-15

    Biases toward processing negative versus positive information vary as a function of level of awareness, and are modulated by monoamines. Excessive biases are associated with individual differences in mood and emotional stability, and emotional disorder. Here, we examined the impact of the catechol-O-methyltransferase (COMT) Val(108/158)Met polymorphism, involved in dopamine and norepinephrine catabolism, on both emotional brain function and self-reported negativity bias. COMT genotyping and self-reported level of negativity bias were completed for 46 healthy participants taking part in the Brain Resource International Database. Functional MRI was undertaken during perception of facial expressions of fear and happiness presented under unmasked (consciously identified) and masked (to prevent conscious detection) conditions. Structural MR images were also acquired. A greater number of COMT Met alleles predicted increased activation in brainstem, amygdala, basal ganglia and medial prefrontal regions for conscious fear, but decreased activation for conscious happiness. This pattern was also apparent for brainstem activation for the masked condition. Effects were most apparent for females. These differences could not be explained by gray matter variations. The Met-related profile of activation, particularly prefrontally, predicted greater negativity bias associated with risk for emotional disorder. The findings suggest that the COMT Met allele modulates neural substrates of negative versus positive emotion processing. This effect may contribute to negativity biases, which confer susceptibility for emotional disorders. Copyright 2010 Elsevier Inc. All rights reserved.

  2. COMT Val158Met polymorphism, cognitive stability and cognitive flexibility: an experimental examination

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    Rosa Elise C

    2010-09-01

    Full Text Available Abstract Background Dopamine in prefrontal cortex (PFC modulates core cognitive processes, notably working memory and executive control. Dopamine regulating genes and polymorphisms affecting PFC - including Catechol-O-Methyltransferase (COMT Val158Met - are crucial to understanding the molecular genetics of cognitive function and dysfunction. A mechanistic account of the COMT Val158Met effect associates the Met allele with increased tonic dopamine transmission underlying maintenance of relevant information, and the Val allele with increased phasic dopamine transmission underlying the flexibility of updating new information. Thus, consistent with some earlier work, we predicted that Val carriers would display poorer performance when the maintenance component was taxed, while Met carriers would be less efficient when rapid updating was required. Methods Using a Stroop task that manipulated level of required cognitive stability and flexibility, we examined reaction time performance of patients with schizophrenia (n = 67 and healthy controls (n = 186 genotyped for the Val/Met variation. Results In both groups we found a Met advantage for tasks requiring cognitive stability, but no COMT effect when a moderate level of cognitive flexibility was required, or when a conflict cost measure was calculated. Conclusions Our results do not support a simple stability/flexibility model of dopamine COMT Val/Met effects and suggest a somewhat different conceptualization and experimental operationalization of these cognitive components.

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

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    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.

  4. 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.

  5. COMT and MTHFR polymorphisms interaction on cognition in schizophrenia: an exploratory study.

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    Kontis, Dimitrios; Theochari, Eirini; Fryssira, Helen; Kleisas, Spyridon; Sofocleous, Christalena; Andreopoulou, Angeliki; Kalogerakou, Stamatina; Gazi, Anthia; Boniatsi, Lucia; Chaidemenos, Alexandros; Tsaltas, Eleftheria

    2013-03-14

    The investigation of the catechol-O-methyltransferase (COMT-[rs4680]) and methylenetetrahydrofolate reductase (MTHFR-[rs1801133]) polymorphisms' interaction might shed light into the pathogenetic mechanisms of the cognitive dysfunction in schizophrenia. In an exploratory study, we hypothesized that the MTHFR 677T allele which has been related to a hypoactive MTHFR enzyme would augment the unfavorable effects of COMT Val158 homozygosity which has been associated with COMT enzyme hyperfunction. 90 schizophrenia patients and 55 healthy volunteers were assessed on psychomotor speed, pattern and spatial recognition memory (SRM), spatial working memory (SWM), attentional flexibility and planning (Stockings of Cambridge-SOC). IQ scores in a random subgroup of patients were also measured. A significant COMT×MTHFR interaction on SWM (p=0.048) and planning (p=0.026) was revealed in both groups. Among COMT-Val/Val participants, MTHFR-C/C made more SWM errors (p=0.033) and solved fewer SOC problems (p=0.025) than MTHFR-T carriers. In patients, there was a significant COMT×MTHFR interaction on full scale IQ (p=0.035): among COMT-Met carriers, MTHFR-T carriers performed significantly worse than MTHFR-C/C (p=0.021), which was driven by a COMT×MTHFR interaction involving performance IQ (p=0.047). In conclusion, COMT and MTHFR polymorphisms interacted on cognition, suggesting that the MTHFR enzyme activity might moderate the effects of the COMT enzyme. In contrast to our initial hypothesis, the MTHFR T-allele attenuated the cognitive effects of COMT Val homozygosity. In this preliminary study, we propose that dopaminergic and intracellular methylation mechanisms could interact on cognitive deficits in schizophrenia. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  6. Executive control in schizophrenia: a preliminary study on the moderating role of COMT Val158Met for comorbid alcohol and substance use disorders.

    Science.gov (United States)

    Carrà, Giuseppe; Nicolini, Gabriella; Crocamo, Cristina; Lax, Annamaria; Amidani, Francesca; Bartoli, Francesco; Castellano, Filippo; Chiorazzi, Alessia; Gamba, Giulia; Papagno, Costanza; Clerici, Massimo

    2017-07-01

    A functional polymorphism in the catechol-O-methyltransferase (COMT) gene (Val158Met) appears to influence cognition in people with alcohol/substance use disorders (AUD/SUD) and in those with psychosis. To explore the potential moderating effect of these factors, a cross-sectional study was conducted, randomly recruiting subjects with DSM-IV diagnosis of schizophrenia. AUD/SUD was rigorously assessed, as well as COMT Val158Met polymorphism. Executive control functioning was measured using the Intra-Extra Dimensional Set Shift (IED). The effect of a possible interaction between comorbid AUD/SUD and COMT Val158Met polymorphism on IED scores was explored. Subjects with schizophrenia, comorbid AUD/SUD, and MetMet carriers for SNP rs4680 of the COMT gene showed worse performance on IED completed stages scores, as compared with individuals with ValVal genotype. However, among subjects without AUD/SUD, those with the MetMet variant performed better than people carrying ValVal genotype. This study is the first to date examining the impact of COMT on cognition in a highly representative sample of people with schizophrenia and comorbid AUD/SUD. Differential moderating effects of COMT Val/Met genotype variations may similarly influence executive functions in people with schizophrenia and comorbid AUD/SUD.

  7. Schooling and variation in the COMT gene: the devil is in the details.

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    Campbell, Daniel; Bick, Johanna; Yrigollen, Carolyn M; Lee, Maria; Joseph, Antony; Chang, Joseph T; Grigorenko, Elena L

    2013-10-01

    Schooling is considered one of the major contributors to the development of intelligence within societies and individuals. Genetic variation might modulate the impact of schooling and explain, at least partially, the presence of individual differences in classrooms. We studied a sample of 1,502 children (mean age = 11.7 years) from Zambia. Approximately 57% of these children were enrolled in school, and the rest were not. To quantify genetic variation, we investigated a number of common polymorphisms in the catechol-O-methyltransferase (COMT) gene that controls the production of the protein thought to account for >60% of the dopamine degradation in the prefrontal cortex. Haplotype analyses generated results ranging from the presence to absence of significant interactions between a number of COMT haplotypes and indicators of schooling (i.e., in- vs. out-of-school and grade completed) in the prediction of nonverbal intelligence, depending on the parameter specification. However, an investigation of the distribution of corresponding p-values suggested that these positive results were false. Convincing evidence that the variation in the COMT gene is associated with individual differences in nonverbal intelligence either directly or through interactions with schooling was not found. p-values produced by the method of testing for haplotype effects employed here may be sensitive to parameter settings, invalid under default settings, and should be checked for validity through simulation. © 2013 The Authors. Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.

  8. Different Roles of COMT and HTR2A Genotypes in Working Memory Subprocesses.

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    Hirohito M Kondo

    Full Text Available Working memory is linked to the functions of the frontal areas, in which neural activity is mediated by dopaminergic and serotonergic tones. However, there is no consensus regarding how the dopaminergic and serotonergic systems influence working memory subprocesses. The present study used an imaging genetics approach to examine the interaction between neurochemical functions and working memory performance. We focused on functional polymorphisms of the catechol-O-methyltransferase (COMT Val(158Met and serotonin 2A receptor (HTR2A -1438G/A genes, and devised a delayed recognition task to isolate the encoding, retention, and retrieval processes for visual information. The COMT genotypes affected recognition accuracy, whereas the HTR2A genotypes were associated with recognition response times. Activations specifically related to working memory were found in the right frontal and parietal areas, such as the middle frontal gyrus (MFG, inferior frontal gyrus (IFG, anterior cingulate cortex (ACC, and inferior parietal lobule (IPL. MFG and ACC/IPL activations were sensitive to differences between the COMT genotypes and between the HTR2A genotypes, respectively. Structural equation modeling demonstrated that stronger connectivity in the ACC-MFG and ACC-IFG networks is related to better task performance. The behavioral and fMRI results suggest that the dopaminergic and serotonergic systems play different roles in the working memory subprocesses and modulate closer cooperation between lateral and medial frontal activations.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Facial emotion recognition in schizophrenia: An exploratory study on the role of comorbid alcohol and substance use disorders and COMT Val158Met.

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    Carrà, Giuseppe; Nicolini, Gabriella; Lax, Annamaria; Bartoli, Francesco; Castellano, Filippo; Chiorazzi, Alessia; Gamba, Giulia; Bava, Mattia; Crocamo, Cristina; Papagno, Costanza

    2017-11-01

    To explore whether facial emotion recognition (FER), impaired in both schizophrenia and alcohol and substance use disorders (AUDs/SUDs), is additionally compromised among comorbid subjects, also considering the role of catechol-O-methyltransferase (COMT) Val158Met. We conducted a cross-sectional study, randomly recruiting 67 subjects with a DSM-IV-TR diagnosis of schizophrenia, and rigorously assessing AUDs/SUDs and COMT Val158Met polymorphism. FER was assessed using the Ekman 60 Faces Test- EK-60F. As a whole, the sample scored significantly lower than normative data on EK-60F. However, subjects with comorbid AUDs/SUDs did not perform worse on EK-60F than those without, who had a better performance on EK-60F if they carried the COMT Val/Met variant. This study is the first to date examining the impact of AUDs/SUDs and COMT variants on FER in an epidemiologically representative sample of subjects with schizophrenia. Our findings do not suggest an additional impairment from comorbid AUDs/SUDs on FER among subjects with schizophrenia, whilst COMT Val158Met, though based on a limited sample, might have a role just among those without AUDs/SUDs. Based on our results, additional research is needed also exploring differential roles of various substances. Copyright © 2017 John Wiley & Sons, Ltd.

  11. Association between the COMT Val158Met polymorphism and fibromyalgia susceptibility and fibromyalgia impact questionnaire score: a meta-analysis.

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    Lee, Young Ho; Kim, Jae-Hoon; Song, Gwan Gyu

    2015-01-01

    The aim of this study was to explore whether the catechol-O-methyltransferase (COMT) Val158Met polymorphism is associated with susceptibility to fibromyalgia and fibromyalgia impact questionnaire (FIQ) score in fibromyalgia patients. We conducted a meta-analysis of the associations of the COMT Val158Met polymorphism with fibromyalgia risk as well as FIQ score in fibromyalgia patients. A total of 993 fibromyalgia patients and 778 controls from 10 studies on the COMT Val158Met polymorphism and 538 fibromyalgia patients from 5 studies on the COMT Val158Met polymorphism and FIQ score were included in this meta-analysis. The meta-analysis revealed an association between fibromyalgia and the COMT Met/Met + Val/Met genotype in all study subjects (odds ratio (OR) 1.635, 95 % confidence interval (CI) 1.029-2.597, p = 0.037). However, stratification by ethnicity indicated no association between the Met/Met + Val/Met genotype and fibromyalgia in the European and Turkish populations (OR 1.202, 95 % CI 0.876-1.649, p = 0.255; OR 2.132, 95 % CI 0.764-5.949, p = 0.148, respectively). Analysis using other genetic models showed no association between the COMT Val158Met polymorphism and fibromyalgia. The meta-analysis also revealed that the FIQ score was significantly higher in individuals with the COMT Met/Met genotype than in those with the Val/Val genotype [weighted mean difference (WMD) = 14.39, 95 % CI 3.316-25.48, p = 0.011] and the Val/Met genotype (WMD = 5.108, 95 % CI 2.212-4.891, p = 0.021). This meta-analysis identified an association between fibromyalgia risk and the COMT Val158Met polymorphism as well as the FIQ score in fibromyalgia patients.

  12. Nonlinear modulation of interacting between COMT and depression on brain function.

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    Gong, L; He, C; Yin, Y; Ye, Q; Bai, F; Yuan, Y; Zhang, H; Lv, L; Zhang, H; Zhang, Z; Xie, C

    2017-09-01

    The catechol-O-methyltransferase (COMT) gene is related to dopamine degradation and has been suggested to be involved in the pathogenesis of major depressive disorder (MDD). However, how this gene affects brain function properties in MDD is still unclear. Fifty patients with MDD and 35 cognitively normal participants underwent a resting-state functional magnetic resonance imaging scan. A voxelwise and data-drive global functional connectivity density (gFCD) analysis was used to investigate the main effects and the interactions of disease states and COMT rs4680 gene polymorphism on brain function. We found significant group differences of the gFCD in bilateral fusiform area (FFA), post-central and pre-central cortex, left superior temporal gyrus (STG), rectal and superior temporal gyrus and right ventrolateral prefrontal cortex (vlPFC); abnormal gFCDs in left STG were positively correlated with severity of depression in MDD group. Significant disease×COMT interaction effects were found in the bilateral calcarine gyrus, right vlPFC, hippocampus and thalamus, and left SFG and FFA. Further post-hoc tests showed a nonlinear modulation effect of COMT on gFCD in the development of MDD. Interestingly, an inverted U-shaped modulation was found in the prefrontal cortex (control system) but U-shaped modulations were found in the hippocampus, thalamus and occipital cortex (processing system). Our study demonstrated nonlinear modulation of the interaction between COMT and depression on brain function. These findings expand our understanding of the COMT effect underlying the pathophysiology of MDD. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

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

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    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 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 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 effects of psychological stress on TMD pain, highlighting that effects are most pronounced in individuals whose genetic susceptibility increases responsiveness to catecholamine neurotransmitters. © International & American Associations for Dental Research 2015.

  14. Val158Met polymorphism in the COMT gene is associated with hypersomnia and mental health-related quality of life in a Colombian sample.

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    Jiménez, Karen M; Pereira-Morales, Angela J; Forero, Diego A

    2017-03-22

    The identification of genes that are risk factors for major depressive disorder remains a main task for global psychiatric research. The Catechol-O-methyltransferase (COMT) gene has been an important candidate risk factor for several psychiatric disorders. Previous studies have shown that a functional polymorphism (Val158Met) in this gene has an effect on several brain circuits and endophenotypes of psychiatric relevance. The aim of this study was to explore the association of a functional polymorphism in the COMT gene with psychological distress, sleep problems and health-related quality of life. Two hundred seventy young Colombian subjects (mean age: 21.3 years; range: 18-57 years) completed the Patient Health Questionnaire-9, the Perceived Stress Scale, the Oviedo Sleep Questionnaire and the 12-Item Short-Form Health Survey and were genotyped for the Val158Met polymorphism (rs4680) in the COMT gene. A linear regression analysis, adjusting for potential confounding factors, was carried out. Subjects that were Met carriers (Val/Met and Met/Met genotypes) showed higher scores for hypersomnia (p=0.001) and lower scores for mental health-related quality of life (p=0.007), these associations remained significant after correcting for multiple testing. These findings support the hypothesis of a broad effect of the Val158Met polymorphism in the COMT gene on several dimensions of behavior and neuropsychiatric symptoms. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. The effect of COMT Val158 Met genotype on decision-making and preliminary findings on its interaction with the 5-HTTLPR in healthy females.

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    van den Bos, Ruud; Homberg, Judith; Gijsbers, Ellen; den Heijer, Esther; Cuppen, Edwin

    2009-02-01

    Poor decision-making is inherent to several psychiatric conditions for which a genetic basis may exist. We previously showed that healthy female volunteers homozygous for the short allele (s/s) of the serotonin transporter length polymorphic region (5-HTTLPR) chose more often cards from disadvantageous decks in the Iowa Gambling Task (IGT), which measures decision-making, than long (l) allele carriers. The 5-HTTLPR and catechol-O-methyltransferase (COMT) Val(158) Met polymorphism affect the same set of neuronal structures. Therefore, we explored the effect of the (COMT) Val(158) Met polymorphism on IGT performance and its interaction with the 5-HTTLPR in the same subjects in this study. We observed that subjects homozygous for methionine (Met/Met) chose more disadvantageously than subjects homozygous for valine (Val/Val). s/s-Met/Met-subjects appeared to show the poorest IGT performance of all possible combinations of 5-HTTLPR and COMT allelic variants. Using the Expectancy-Valence model, no differences were found for the three different 5-HTTLPR or COMT genotypes regarding (i) attention to wins versus losses, (ii) updating rate, or (iii) response consistency. However, subjects with at least one Met-allele were paying more attention to wins than subjects with no Met-alleles. We discuss whether a common neuronal mechanism relates to s- and Met-allele-related deficits in updating and/or processing of choice outcome to guide subsequent choices in this gamble-based test.

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Association analysis of COMT/MTHFR polymorphisms and major depressive disorder in Chinese Han population.

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    Shen, Xinhua; Wu, Yanfeng; Guan, Tiefeng; Wang, Xiaoquan; Qian, Mincai; Lin, Min; Shen, Zhongxia; Sun, Jushui; Zhong, Hua; Yang, Jianhong; Li, Liang; Yuan, Yonggui

    2014-06-01

    In several previous biochemical and genetic studies, the Val158Met polymorphism of the gene encoding catechol-O-methyltransferase (COMT) and the C677T polymorphism of Methylenetetrahydrofolate reductase (MTHFR) have been suggested to be involved in the pathogenesis as well as the treatment response of major depressive disorder (MDD), but the results have been inconsistent. In this study, we investigate the association of COMT/MTHFR and their interactions with MDD and antidepressant response in Chinese Han population. Three hundred and sixty eight depressed patients who met DSM-IV criteria for MDD were recruited for the study. Two hundred and nineteen normal controls were recruited from the local community. Patients and normal controls were genotyped for the functional COMT val158met and MTHFR C677T polymorphisms. Patients were characterized for clinical response to antidepressant treatment as measured by intra-individual changes of Hamilton Depression (HAMD-17) scores over 6 weeks. The T allele (OR=1.81; CI95%=1.40-2.34, Pdepressed individuals than among controls (OR=1.52, CI95%=1.04-2.21, P=0.02). There is disequilibrium in age and sex between case and control groups. Though we control the two variables in the statistic analysis, to be more accurate, we need to increase sample size in further study. Individuals with the genotype COMT Met/Val and MTHFR C/T have more probability of suffering from MDD. However, there is no association between gene polymorphism and treatment response. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Modulating effect of COMT Val(158)Met polymorphism on interference resolution during a working memory task.

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    Jaspar, Mathieu; Dideberg, Vinciane; Bours, Vincent; Maquet, Pierre; Collette, Fabienne

    2015-04-01

    Genetic variability related to the catechol-O-methyltransferase (COMT) gene has received increasing attention in the last 15years, in particular as a potential modulator of the neural substrates underlying inhibitory processes and updating in working memory (WM). In an event-related functional magnetic resonance imaging (fMRI) study, we administered a modified version of the Sternberg probe recency task (Sternberg, 1966) to 43 young healthy volunteers, varying the level of interference across successive items. The task was divided into two parts (high vs. low interference) to induce either proactive or reactive control processes. The participants were separated into three groups according to their COMT Val(158)Met genotype [Val/Val (VV); Val/Met (VM); Met/Met (MM)]. The general aim of the study was to determine whether COMT polymorphism has a modulating effect on the neural substrates of interference resolution during WM processing. Results indicate that interfering trials were associated with greater involvement of frontal cortices (bilateral medial frontal gyrus, left precentral and superior frontal gyri, right inferior frontal gyrus) in VV homozygous subjects (by comparison to Met allele carriers) only in the proactive condition of the task. In addition, analysis of peristimulus haemodynamic responses (PSTH) revealed that the genotype-related difference observed in the left SFG was specifically driven by a larger increase in activity from the storage to the recognition phase of the interfering trials in VV homozygous subjects. These results confirm the impact of COMT genotype on inhibitory processes during a WM task, with an advantage for Met allele carriers. Interestingly, this impact on frontal areas is present only when the level of interference is high, and especially during the transition from storage to recognition in the left superior frontal gyrus. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Perceived Stress in Adults Aged 65 to 90: Relations to Facets of Time Perspective and COMT Val158Met Polymorphism.

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    Rönnlund, Michael; Åström, Elisabeth; Adolfsson, Rolf; Carelli, Maria G

    2018-01-01

    This study examined the relation between perceived stress and time perspective (views of past, present, future) in a population-based sample of older adults (65-90 years, N = 340). The Perceived Questionnaire (PSQ index) was used to measure stress and the Swedish version of the Zimbardo Time Perspective Inventory (S-ZTPI) was used to operationalize time perspective. Unlike the original inventory, S-ZTPI separates positive and negative aspects of a future time perspective and we hypothesized that the Future Negative (FN) scale would be important to account for variations in stress. Additionally, associations with Catechol-O-methyltransferase ( COMT ) Val 158 Met polymorphism were examined, motivated by prior associations of this single nucleotide polymorphism (SNP) with stress (or "anxiety") related personality traits. In line with the hypotheses, FN was the strongest predictor of PSQ index scores in multiple regression analyses. In a related vein, the dichotomization of the unitary Future scale increased the association between PSQ scores and a measure of deviations from a balanced time perspective, i.e., the difference between a proposed optimal and observed ZTPI profile. Finally, higher levels of stress as well as higher scores on FN were observed in COMT Val/Val carriers, at least among men. This suggests a shared dopaminergic genetic influence on these variables. Collectively, the results demonstrate that perceived stress is closely linked to time perspective and highlight the need to take negative aspects of a future temporal orientation into account to understand this relation.

  2. Perceived Stress in Adults Aged 65 to 90: Relations to Facets of Time Perspective and COMT Val158Met Polymorphism

    Directory of Open Access Journals (Sweden)

    Michael Rönnlund

    2018-03-01

    Full Text Available This study examined the relation between perceived stress and time perspective (views of past, present, future in a population-based sample of older adults (65–90 years, N = 340. The Perceived Questionnaire (PSQ index was used to measure stress and the Swedish version of the Zimbardo Time Perspective Inventory (S-ZTPI was used to operationalize time perspective. Unlike the original inventory, S-ZTPI separates positive and negative aspects of a future time perspective and we hypothesized that the Future Negative (FN scale would be important to account for variations in stress. Additionally, associations with Catechol-O-methyltransferase (COMT Val158Met polymorphism were examined, motivated by prior associations of this single nucleotide polymorphism (SNP with stress (or “anxiety” related personality traits. In line with the hypotheses, FN was the strongest predictor of PSQ index scores in multiple regression analyses. In a related vein, the dichotomization of the unitary Future scale increased the association between PSQ scores and a measure of deviations from a balanced time perspective, i.e., the difference between a proposed optimal and observed ZTPI profile. Finally, higher levels of stress as well as higher scores on FN were observed in COMT Val/Val carriers, at least among men. This suggests a shared dopaminergic genetic influence on these variables. Collectively, the results demonstrate that perceived stress is closely linked to time perspective and highlight the need to take negative aspects of a future temporal orientation into account to understand this relation.

  3. The COMT Val158Met Polymorphism Is Associated With Response to Add-on Dextromethorphan Treatment in Bipolar Disorder.

    Science.gov (United States)

    Lee, Sheng-Yu; Chen, Shiou-Lan; Wang, Tzu-Yun; Chang, Yun-Hsuan; Chen, Po See; Huang, San-Yuan; Tzeng, Nian-Sheng; Wang, Liang-Jen; Lee, I Hui; Chen, Kao Ching; Yang, Yen Kuang; Lu, Ru-Band

    2017-02-01

    We previously conducted a randomized, double-blind, controlled, 12-week study evaluating the effect of add-on dextromethorphan (DM), a noncompetitive N-methyl-D-aspartate receptor antagonist, on patients with bipolar disorder (BD) treated using valproate (VPA), which showed negative clinical differences. The genetic variation between each individual may be responsible for interindividual differences. The catechol-O-methyltransferase (COMT) gene has been a candidate gene for BD. In the current study, we investigated whether the COMT Val158Met polymorphism predicts treatment response to VPA + add-on DM and to VPA + placebo. Patients with BD (n = 309) undergoing regular VPA treatments were randomly assigned to groups given either add-on DM (30 mg/d) (n = 102), DM (60 mg/d) (n = 101), or placebo (n = 106) for 12 weeks. The Hamilton Depression Rating Scale and Young Mania Rating Scale were used to evaluate clinical response during weeks 0, 1, 2, 4, 8, and 12. The genotypes of the COMT Val158Met polymorphism were determined using polymerase chain reaction plus restriction fragment length polymorphism analysis. To adjust for within-subject dependence over repeated assessments, multiple linear regression with generalized estimating equation methods was used. When stratified by the COMT Val158Met genotypes, significantly greater decreases in Hamilton Depression Rating Scale scores were found in the VPA + DM (30 mg/d) group in patients with the Val/Met genotype (P = 0.008). We conclude that the COMT Val158Met polymorphism may influence responses to DM (30 mg/d) by decreasing depressive symptoms in BD patients.

  4. The relation of serotonin-related gene and COMT gene polymorphisms with criminal behavior in schizophrenic disorder.

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    Koh, Kyung Bong; Choi, Eun Hee; Lee, Young-joon; Han, Mooyoung; Choi, Sang-Sup; Kim, So Won; Lee, Min Goo

    2012-02-01

    It has been suggested that patients with schizophrenia might be involved in criminal behavior, such as homicidal and violent behavior. However, the relationship between criminal behavior and genes in patients with schizophrenia has not been clearly elucidated. The objective of this study was to examine the relation between criminal behavior and serotonin-related gene or catechol-O-methyltransferase (COMT) gene polymorphisms in patients with schizophrenia. Serotonin-related and COMT polymorphic markers were assessed by using single nucleotide polymorphism (SNP) genotyping. Ninety-nine crime-related inpatients with schizophrenia (57 homicidal and 42 nonhomicidal violent) and 133 healthy subjects were enrolled between October 2005 and May 2008. Diagnoses were made according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. The genotype frequencies of tryptophan hydroxylase-1 (TPH1) A218C and COMT V158M were compared between groups. The TPH1 CC genotype had 2.7-fold higher odds of crime-related schizophrenia compared with A-carrier genotype after the analysis was controlled for sex and age (OR, 2.69; 95% CI, 1.22 - 5.91; P = .01). In addition, the TPH1 CC genotype had 3.4-fold higher odds of homicidal schizophrenia compared with A-carrier genotype after the analysis was controlled for sex and age (OR, 3.38; 95% CI, 1.40 - 8.18; P = .007). However, no significant differences were found in the frequencies of genotype of COMT polymorphism between criminal schizophrenics and healthy subjects, nor were any significant differences found between nonhomicidal schizophrenics and healthy subjects. These results indicate that the TPH1 CC recessive genotype is likely to be a genetic risk factor for criminal behavior, especially homicidal behavior in patients with schizophrenia. However, COMT gene polymorphisms were not associated with criminal behavior in schizophrenic patients. © Copyright 2012 Physicians Postgraduate Press, Inc.

  5. COMT Val158Met polymorphism is associated with post-traumatic stress disorder and functional outcome following mild traumatic brain injury.

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    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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Pathways to age of onset of heroin use: a structural model approach exploring the relationship of the COMT gene, impulsivity and childhood trauma.

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    Li, Ting; Du, Jiang; Yu, Shunying; Jiang, Haifeng; Fu, Yingmei; Wang, Dongxiang; Sun, Haiming; Chen, Hanhui; Zhao, Min

    2012-01-01

    The interaction of the association of dopamine genes, impulsivity and childhood trauma with substance abuse remains unclear. 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. 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. 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. 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.

  7. 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

  8. COMT Val158Met polymorphism moderates the association between PTSD symptom severity and hippocampal volume.

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    Hayes, Jasmeet P; Logue, Mark W; Reagan, Andrew; Salat, David; Wolf, Erika J; Sadeh, Naomi; Spielberg, Jeffrey M; Sperbeck, Emily; Hayes, Scott M; McGlinchey, Regina E; Milberg, William P; Verfaellie, Mieke; Stone, Annjanette; Schichman, Steven A; Miller, Mark W

    2017-03-01

    Memory-based alterations are among the hallmark symptoms of posttraumatic stress disorder (PTSD) and may be associated with the integrity of the hippocampus. However, neuroimaging studies of hippocampal volume in individuals with PTSD have yielded inconsistent results, raising the possibility that various moderators, such as genetic factors, may influence this association. We examined whether the catechol-O-methyltransferase (COMT) Val158Met polymorphism, which has previously been shown to be associated with hippocampal volume in healthy individuals, moderates the association between PTSD and hippocampal volume. Recent war veterans underwent structural MRI on a 3 T scanner. We extracted volumes of the right and left hippocampus using FreeSurfer and adjusted them for individual differences in intracranial volume. We assessed PTSD severity using the Clinician-Administered PTSD Scale. Hierarchical linear regression was used to model the genotype (Val158Met polymorphism) × PTSD severity interaction and its association with hippocampal volume. We included 146 white, non-Hispanic recent war veterans (90% male, 53% with diagnosed PTSD) in our analyses. A significant genotype × PTSD symptom severity interaction emerged such that individuals with greater current PTSD symptom severity who were homozygous for the Val allele showed significant reductions in left hippocampal volume. The direction of proposed effects is unknown, thus precluding definitive assessment of whether differences in hippocampal volume reflect a consequence of PTSD, a pre-existing characteristic, or both. Our findings suggest that the COMT polymorphism moderates the association between PTSD and hippocampal volume. These results highlight the role that the dopaminergic system has in brain structure and suggest a possible mechanism for memory disturbance in individuals with PTSD.

  9. Time-resolved influences of functional DAT1 and COMT variants on visual perception and post-processing.

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    Stephan Bender

    Full Text Available BACKGROUND: Dopamine plays an important role in orienting and the regulation of selective attention to relevant stimulus characteristics. Thus, we examined the influences of functional variants related to dopamine inactivation in the dopamine transporter (DAT1 and catechol-O-methyltransferase genes (COMT on the time-course of visual processing in a contingent negative variation (CNV task. METHODS: 64-channel EEG recordings were obtained from 195 healthy adolescents of a community-based sample during a continuous performance task (A-X version. Early and late CNV as well as preceding visual evoked potential components were assessed. RESULTS: Significant additive main effects of DAT1 and COMT on the occipito-temporal early CNV were observed. In addition, there was a trend towards an interaction between the two polymorphisms. Source analysis showed early CNV generators in the ventral visual stream and in frontal regions. There was a strong negative correlation between occipito-temporal visual post-processing and the frontal early CNV component. The early CNV time interval 500-1000 ms after the visual cue was specifically affected while the preceding visual perception stages were not influenced. CONCLUSIONS: Late visual potentials allow the genomic imaging of dopamine inactivation effects on visual post-processing. The same specific time-interval has been found to be affected by DAT1 and COMT during motor post-processing but not motor preparation. We propose the hypothesis that similar dopaminergic mechanisms modulate working memory encoding in both the visual and motor and perhaps other systems.

  10. Modification of depression by COMT val158met polymorphism in children exposed to early severe psychosocial deprivation

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    Drury, Stacy S; Theall, Katherine P; Smyke, Anna T; Keats, Bronya JB; Egger, Helen L; Nelson, Charles A; Fox, Nathan A; Marshall, Peter J; Zeanah, Charles H

    2014-01-01

    Objective To examine the impact of the Catechol-O-Methyltransferase (COMT) val158met allele on depressive symptoms in young children exposed to early severe social deprivation as a result of being raised in institutions. Methods 136 children from the Bucharest Early Intervention Project (BEIP) were randomized before 31 months of age to either care as usual (CAU) in institutions or placement in newly created foster care (FCG). At 54 months of age, a psychiatric assessment using the Preschool Age Psychiatric Assessment (PAPA) was completed. DNA was collected and genotyped for the COMT val158met polymorphism. Multivariate analysis examined the relationship between COMT alleles and depressive symptoms. Results Mean level of depressive symptoms was lower among participants with the met allele compared to those with two copies of the val allele (p <0.05). Controlling for group and gender, the rate of depressive symptoms was significantly lower among participants with the met/met or the met/val genotype (adjusted relative risk (aRR) = 0.67, 95% CI = 0.45, 0.99) compared to participants with the val/val genotype, indicating an intermediate impact for heterozygotes consistent with the biological impact of this polymorphism. The impact of genotype within groups differed significantly. There was a significant protective effect of the met allele on depressive symptoms within the CAU group, however there was no relationship seen within the FCG group. Conclusions This is the first study, to our knowledge, to find evidence of a gene × environment interaction in the setting of early social deprivation. These results support the hypothesis that individual genetic differences may explain some of the variability in recovery amongst children exposed to early severe social deprivation. PMID:20403637

  11. COMT Val158 Met moderates the link between rank and aggression in a non-human primate.

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    Gutleb, D R; Roos, C; Noll, A; Ostner, J; Schülke, O

    2018-04-01

    The COMT Val 158 Met polymorphism is one of the most widely studied genetic polymorphisms in humans implicated in aggression and the moderation of stressful life event effects. We screened a wild primate population for polymorphisms at the COMT Val 158 Met site and phenotyped them for aggression to test whether the human polymorphism exists and is associated with variation in aggressive behavior. Subjects were all adults from 4 study groups (37 males, 40 females) of Assamese macaques (Macaca assamensis) in their natural habitat (Phu Khieo Wildlife Sanctuary, Thailand). We collected focal animal behavioral data (27 males, 36 females, 5964 focal hours) and fecal samples for non-invasive DNA analysis. We identified the human COMT Val 158 Met polymorphism (14 Met/Met, 41 Val/Met and 22 Val/Val). Preliminary results suggest that COMT genotype and dominance rank interact to influence aggression rates. Aggression rates increased with rank in Val/Val, but decreased in Met/Met and Val/Met individuals, with no significant main effect of COMT genotype on aggression. Further support for the interaction effect comes from time series analyses revealing that when changing from lower to higher rank position Val/Val individuals decreased, whereas Met/Met individuals increased their aggression rate. Contradicting the interpretation of earlier studies, we show that the widely studied Val 158 Met polymorphism in COMT is not unique to humans and yields similar behavioral phenotypes in a non-human primate. This study represents an important step towards understanding individual variation in aggression in a wild primate population and may inform human behavioral geneticists about the evolutionary roots of inter-individual variation in aggression. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  12. The association between COMT rs4680 and 5-HTTLPR genotypes and concussion history in South African rugby union players.

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    Mc Fie, Sarah; Abrahams, Shameemah; Patricios, Jon; Suter, Jason; Posthumus, Michael; September, Alison V

    2018-04-01

    The objective was to investigate the relationship between Catechol-O-methyltransferase (COMT) rs4680 and serotonin-transporter-linked polymorphic region (5-HTTLPR) genotypes with concussion history and personality traits. Rugby players ("all levels": n = 303), from high schools ("junior", n = 137), senior amateur, and professional teams ("senior", n = 166), completed a self-reported concussion history questionnaire, Cloninger's Tridimensional Personality Questionnaire, and donated a DNA sample. Participants were allocated into control (non-concussed, n = 140), case (all) (previous suspected or diagnosed concussions, n = 163), or case (diagnosed only) (previous diagnosed concussion, n = 140) groups. COMT rs4680 Val/Val genotypes were over-represented in controls in all levels (P = 0.013, OR:2.00, 95% CI:1.15-3.57) and in juniors (P = 0.003, OR:3.57, 95% CI:1.45-9.09). Junior Val/Val participants displayed increased "anticipatory worry" (P = 0.023). The 5-HTTLPR low expressing group was under-represented in controls when all levels were considered (P = 0.032; OR:2.02, 95% CI:1.05-3.90) and in juniors (P = 0.021; OR:3.36, 95% CI:1.16-9.72). Junior 5-HTTLPR low and intermediate expressing groups displayed decreased "harm avoidance" (P = 0.009), "anticipatory worry" (P = 0.041), and "fear of uncertainty" (P < 0.001). This study provides preliminary indications that personality associated genetic variants can influence concussion in rugby.

  13. Estradiol replacement enhances fear memory formation, impairs extinction and reduces COMT expression levels in the hippocampus of ovariectomized female mice.

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    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.

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

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    Ghisari, Mandana; Long, Manhai; Bonefeld-Jørgensen, Eva C

    2013-01-01

    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. 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. 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. Our data provide new information on gene polymorphisms in Greenlandic Inuit that might support evaluation of susceptibility to environmental contaminants and warrant further studies.

  15. The effect of COMT Val158Met and DRD2 C957T polymorphisms on executive function and the impact of early life stress.

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    Klaus, Kristel; Butler, Kevin; Durrant, Simon J; Ali, Manir; Inglehearn, Chris F; Hodgson, Timothy L; Gutierrez, Humberto; Pennington, Kyla

    2017-05-01

    Previous research has indicated that variation in genes encoding catechol-O-methyltransferase ( COMT ) and dopamine receptor D2 ( DRD2 ) may influence cognitive function and that this may confer vulnerability to the development of mental health disorders such as schizophrenia. However, increasing evidence suggests environmental factors such as early life stress may interact with genetic variants in affecting these cognitive outcomes. This study investigated the effect of COMT Val158Met and DRD2 C957T polymorphisms on executive function and the impact of early life stress in healthy adults. One hundred and twenty-two healthy adult males (mean age 35.2 years, range 21-63) were enrolled in the study. Cognitive function was assessed using Cambridge Neuropsychological Test Automated Battery and early life stress was assessed using the Childhood Traumatic Events Scale (Pennebaker & Susman, 1988). DRD2 C957T was significantly associated with executive function, with CC homozygotes having significantly reduced performance in spatial working memory and spatial planning. A significant genotype-trauma interaction was found in Rapid Visual Information Processing test, a measure of sustained attention, with CC carriers who had experienced early life stress exhibiting impaired performance compared to the CC carriers without early life stressful experiences. There were no significant findings for COMT Val158Met . This study supports previous findings that DRD2 C957T significantly affects performance on executive function related tasks in healthy individuals and shows for the first time that some of these effects may be mediated through the impact of childhood traumatic events. Future work should aim to clarify further the effect of stress on neuronal systems that are known to be vulnerable in mental health disorders and more specifically what the impact of this might be on cognitive function.

  16. Imaging oxytocin x dopamine interactions: An epistasis effect of CD38 and COMT gene variants influences the impact of oxytocin on amygdala activation to social stimuli

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    Carina eSauer

    2013-04-01

    Full Text Available Although oxytocin (OT has become a major target for the investigation of positive social processes, it can be assumed that it exerts its effects in concert with other neurotransmitters. One candidate for such an interaction is dopamine (DA. For both systems, genetic variants have been identified that influence the availability of the particular substance. A variant of the gene coding for the transmembrane protein CD38 (rs3796863, which is engaged in OT secretion, has been associated with OT plasma level. The common catechol-O-methyltransferase (COMT val158met polymorphism is known to influence COMT activity and therefore the degradation of DA. The present study aimed to investigate OTxDA interactions in the context of an OT challenge study. Hence, we tested the influence of the above mentioned genetic variants and their interaction on the activation of different brain regions (amygdala, VTA, ventral striatum and fusiform gyrus during the presentation of social stimuli. In a pharmacological cross-over design 55 participants were investigated under OT and placebo (PLA by means of fMRI.Brain imaging results revealed no significant effects for VTA or ventral striatum. Regarding the fusiform gyrus, we could not find any effects apart from those already described in (Sauer et al., 2012. Analyses of amygdala activation resulted in no gene main effect, no gene x substance interaction but a significant gene x gene x substance interaction. While under PLA the effect of CD38 on bilateral amygdala activation to social stimuli was modulated by the COMT genotype, no such epistasis effect was found under OT. Our results provide evidence for an OTxDA interaction during responses to social stimuli. We postulate that the effect of central OT secretion on amygdala response is modulated by the availability of DA. Therefore, for an understanding of the effect of social hormones on social behavior, interactions of OT with other transmitter systems have to be taken

  17. Childhood Abuse Experiences and the COMT and MTHFR Genetic Variants Associated With Male Sexual Orientation in the Han Chinese Populations: A Case-Control Study.

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    Qin, Jia-Bi; Zhao, Guang-Lu; Wang, Feng; Cai, Yu-Mao; Lan, Li-Na; Yang, Lin; Feng, Tie-Jian

    2018-01-01

    Although it is widely acknowledged that genetic and environmental factors are involved in the development of male homosexuality, the causes are not fully understood. To explore the association and interaction of childhood abuse experiences and genetic variants of the catechol-O-methyltransferase (COMT) and methylenetetrahydrofolate reductase (MTHFR) genes with the development of male homosexuality. A case-control study of 537 exclusively homosexual men and 583 exclusively heterosexual men was conducted, with data collected from March 2013 to August 2015. Data were analyzed using χ 2 tests and logistic regression models. Sociodemographic characteristics, childhood abuse experiences, and polymorphisms of COMT at rs4680, rs4818, and rs6267 and MTHFR at rs1801133. More frequent occurrence of physical (adjusted odds ratio [aOR] = 1.78), emotional (aOR = 2.07), and sexual (aOR = 2.53) abuse during childhood was significantly associated with the development of male homosexuality. The polymorphisms of MTHFR at rs1801133 and COMT at rs4818 also were significantly associated with the development of male homosexuality in the homozygote comparisons (T/T vs C/C at rs1801133, aOR = 1.68; G/G vs C/C at rs4818, aOR = 1.75). In addition, significant interaction effects between childhood abuse experiences and the COMT and MTHFR genetic variants on the development of male homosexuality were found. This is the first time that an association of childhood abuse, COMT and MTHFR genetic variants, and their interactions with development of male homosexuality was exhaustively explored, which could help provide new insight into the etiology of male homosexuality. Because homosexual men are a relatively obscure population, it was impossible to select the study participants by random sampling, which could lead to selection bias. In addition, because this was a case-control study, recall bias was inevitable, and we could not verify causality. Childhood abuse and the COMT and MTHFR genetic

  18. Comparison of the inhibitory effects of tolcapone and entacapone against human UDP-glucuronosyltransferases

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    Lv, Xia [Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023 (China); State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Southern Medical University, Guangzhou 510515 (China); Wang, Xin-Xin [RSKT Biopharma Inc., Dalian 116023 (China); Hou, Jie [Dalian Medical University, Dalian 116044 (China); Fang, Zhong-Ze [RSKT Biopharma Inc., Dalian 116023 (China); Wu, Jing-Jing [Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023 (China); State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Southern Medical University, Guangzhou 510515 (China); Cao, Yun-Feng [RSKT Biopharma Inc., Dalian 116023 (China); Liu, Shu-Wen [State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Southern Medical University, Guangzhou 510515 (China); Ge, Guang-Bo, E-mail: geguangbo@dicp.ac.cn [Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023 (China); State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Southern Medical University, Guangzhou 510515 (China); Yang, Ling, E-mail: ylingdicp@gmail.com [Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023 (China); Jiangxi University of Traditional Chinese Medicine, Nanchang 330006 (China)

    2016-06-15

    Tolcapone and entacapone are two potent catechol-O-methyltransferase (COMT) inhibitors with a similar skeleton and displaying similar pharmacological activities. However, entacapone is a very safe drug used widely in the treatment of Parkinson's disease, while tolcapone is only in limited use for Parkinson's patients and needs careful monitoring of hepatic functions due to hepatotoxicity. This study aims to investigate and compare the inhibitory effects of entacapone and tolcapone on human UDP-glucosyltransferases (UGTs), as well as to evaluate the potential risks from the view of drug-drug interactions (DDI). The results demonstrated that both tolcapone and entacapone exhibited inhibitory effects on UGT1A1, UGT1A7, UGT1A9 and UGT1A10. In contrast to entacapone, tolcapone exhibited more potent inhibitory effects on UGT1A1, UGT1A7, and UGT1A10, while their inhibitory potentials against UGT1A9 were comparable. It is noteworthy that the inhibition constants (K{sub i}) of tolcapone and entacapone against bilirubin-O-glucuronidation in human liver microsomes (HLM) are determined as 0.68 μM and 30.82 μM, respectively, which means that the inhibition potency of tolcapone on UGT1A1 mediated bilirubin-O-glucuronidation in HLM is much higher than that of entacapone. Furthermore, the potential risks of tolcapone or entacapone via inhibition of human UGT1A1 were quantitatively predicted by the ratio of the areas under the plasma drug concentration-time curve (AUC). The results indicate that tolcapone may result in significant increase in AUC of bilirubin or the drugs primarily metabolized by UGT1A1, while entacapone is unlikely to cause a significant DDI through inhibition of UGT1A1. - Highlights: • Tolcapone and entacapone exhibited preferential inhibition against UGT1A enzymes. • In contrast to entacapone, tolcapone exhibited more potent inhibitory effects on human UGT1A1, 1 A7 and 1 A10. • Tolcapone may lead to significant increase in AUC of bilirubin.

  19. COMT Val(158)Met and 5HTTLPR functional loci interact to predict persistence of anxiety across adolescence: results from the Victorian Adolescent Health Cohort Study.

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    Olsson, C A; Byrnes, G B; Anney, R J L; Collins, V; Hemphill, S A; Williamson, R; Patton, G C

    2007-10-01

    We investigated whether a composite genetic factor, based on the combined actions of catechol-O-methyltransferase (COMT) (Val(158)Met) and serotonin transporter (5HTTLPR) (Long-Short) functional loci, has a greater capacity to predict persistence of anxiety across adolescence than either locus in isolation. Analyses were performed on DNA collected from 962 young Australians participating in an eight-wave longitudinal study of mental health and well-being (Victorian Adolescent Health Cohort Study). When the effects of each locus were examined separately, small dose-response reductions in the odds of reporting persisting generalized (free-floating) anxiety across adolescence were observed for the COMT Met(158) [odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.76-0.95, P = 0.004] and 5HTTLPR Short alleles (OR = 0.88, CI = 0.79-0.99, P = 0.033). There was no evidence for a dose-response interaction effect between loci. However, there was a double-recessive interaction effect in which the odds of reporting persisting generalized anxiety were more than twofold reduced (OR = 0.45, CI = 0.29-0.70, P anxiety. Exploratory stratified analyses suggested that genetic protection may be more pronounced under conditions of high stress (insecure attachments and sexual abuse), although strata differences did not reach statistical significance. By describing the interaction between genetic loci, it may be possible to describe composite genetic factors that have a more substantial impact on psychosocial development than individual loci alone, and in doing so, enhance understanding of the contribution of constitutional processes in mental health outcomes.

  20. Stressful life events, perceived stress, and 12-month course of geriatric depression: direct effects and moderation by the 5-HTTLPR and COMT Val158Met polymorphisms.

    Science.gov (United States)

    Zannas, Anthony S; McQuoid, Douglas R; Steffens, David C; Chrousos, George P; Taylor, Warren D

    2012-07-01

    Although the relation between stressful life events (SLEs) and risk of major depressive disorder is well established, important questions remain about the effects of stress on the course of geriatric depression. Our objectives were (1) to examine how baseline stress and change in stress is associated with course of geriatric depression and (2) to test whether polymorphisms of serotonin transporter (5-HTTLPR) and catechol-O-methyltransferase (COMT Val158Met) genes moderate this relation. Two-hundred and sixteen depressed subjects aged 60 years or older were categorized by remission status (Montgomery-Asberg depression rating scale≤6) at 6 and 12 months. At 6 months, greater baseline numbers of self-reported negative and total SLEs and greater baseline perceived stress severity were associated with lower odds of remission. At 12 months, only baseline perceived stress predicted remission. When we examined change in stress, 12-month decrease in negative SLEs and level of perceived stress were associated with improved odds of 12-month remission. When genotype data were included, COMT Val158Met genotype did not influence these relations. However, when compared with 5-HTTLPR L/L homozygotes, S allele carriers with greater baseline numbers of negative SLEs and with greater decrease in negative SLEs were more likely to remit at 12 months. This study demonstrates that baseline SLEs and perceived stress severity may influence the 12-month course of geriatric depression. Moreover, changes in these stress measures over time correlate with depression outcomes. 5-HTTLPR S carriers appear to be more susceptible to both the effects of enduring stress and the benefit of interval stress reduction.

  1. 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

    -posterior thalamic radiation (include optic radiation than the val homozygotes, independent of ADHD diagnosis. Third, children with ADHD had lower FA in the L-CGC and R-retrolenticular part of the internal capsule than the controls, independent of the COMT polymorphism.Conclusion: Significant differences reported here may be evidence that the COMT gene val158met polymorphism variants, as well as ADHD, could affect brain development. ADHD and the COMT polymorphism might be interactively affecting WM development in the R-CGC to alter the WM connectivity in children with val homozygote ADHD.Keywords: neuroimaging, attention deficit, hyperactivity, catechol-O-methyltransferase

  2. Developmental changes in human dopamine neurotransmission: cortical receptors and terminators

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    Rothmond Debora A

    2012-02-01

    Full Text Available Abstract Background Dopamine is integral to cognition, learning and memory, and dysfunctions of the frontal cortical dopamine system have been implicated in several developmental neuropsychiatric disorders. The dorsolateral prefrontal cortex (DLPFC is critical for working memory which does not fully mature until the third decade of life. Few studies have reported on the normal development of the dopamine system in human DLPFC during postnatal life. We assessed pre- and postsynaptic components of the dopamine system including tyrosine hydroxylase, the dopamine receptors (D1, D2 short and D2 long isoforms, D4, D5, catechol-O-methyltransferase, and monoamine oxidase (A and B in the developing human DLPFC (6 weeks -50 years. Results Gene expression was first analysed by microarray and then by quantitative real-time PCR. Protein expression was analysed by western blot. Protein levels for tyrosine hydroxylase peaked during the first year of life (p O-methyltransferase (p = 0.024 were significantly higher in neonates and infants as was catechol-O-methyltransferase protein (32 kDa, p = 0.027. In contrast, dopamine D1 receptor mRNA correlated positively with age (p = 0.002 and dopamine D1 receptor protein expression increased throughout development (p Conclusions We find distinct developmental changes in key components of the dopamine system in DLPFC over postnatal life. Those genes that are highly expressed during the first year of postnatal life may influence and orchestrate the early development of cortical neural circuitry while genes portraying a pattern of increasing expression with age may indicate a role in DLPFC maturation and attainment of adult levels of cognitive function.

  3. Synthesis of two 14C-labeled catechol-o-methyltransferase inhibitors

    International Nuclear Information System (INIS)

    Karlsson, Carita; Honkanen, Erkki

    1991-01-01

    14 C-labelled 3-(3,4-dihydroxy-5-nitrophenylmethylidene)-2,4-pentanedione and 14 C-labelled E-N,N-diethyl-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)acrylamide have been synthesized from [carbonyl- 14 C]vanillin. (author)

  4. Comparison of endothelial progenitor cells in Parkinson's disease patients treated with levodopa and levodopa/COMT inhibitor.

    Directory of Open Access Journals (Sweden)

    Phil Hyu Lee

    Full Text Available BACKGROUND: Levodopa treatment in Parkinson's disease (PD increases in serum homocysteine levels due to its metabolism via catechol O-methyltransferase. Endothelial progenitor cells (EPCs have the capacity to differentiate into mature endothelial cells and are markers for endothelial functions and cardiovascular risks. Along with traditional vascular risk factors, hyperhomocysteinemia is known to decrease the level of EPCs. In the present study, we hypothesized that that levodopa-induced hyperhomocysteinemia leads to a change in EPC levels. METHODOLOGY/PRINCIPAL FINDINGS: We prospectively enrolled PD patients who had been prescribed either levodopa/carbidopa (PD-L group, n = 28 or levodopa/carbidopa/COMT inhibitor (PD-LC group, n = 25 for more than 1 year. The number of circulating EPCs was measured by flow cytometry using dual staining of anti-CD34 and anti-KDR antibodies. The EPCs were divided into tertiles based on their distributions and a logistic regression analysis was used to estimate independent predictors of the highest tertile of EPCs. The number of endothelial progenitor cells was significantly decreased in PD-L patients (118±99/mL compared with either PD-LC patients (269±258/mL, p = 0.007 or controls (206±204/mL, p = 0.012. The level of homocysteine was significantly increased in PD-L patients (14.9±5.3 µmol/L compared with either PD-LC patients (11.9±3.0 µmol/L, p = 0.028 or controls (11.1±2.5 µmol/L, p = 0.012. The level of homocysteine was negatively correlated with endothelial progenitor cell levels (r = -0.252, p = 0.028 and was an independent predictor of the highest tertile of endothelial progenitor cell levels (OR; 0.749 [95% CI: 0.584-0.961]. CONCLUSIONS/SIGNIFICANCE: These data indicate that a higher consumption of EPC for restoration of endothelial damage may be associated with chronic levodopa treatment in PD patients.

  5. Antidepressive-drug-induced bodyweight gain is associated with polymorphisms in genes coding for COMT and TPH1

    DEFF Research Database (Denmark)

    Secher, Anna; Bukh, Jens; Bock, Camilla

    2009-01-01

    of a single depressive episode and who were under antidepressive treatment. Weight gainers were identified based on rating with the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale. Polymorphisms in catechol-O-methyltransferase, tryptophan hydroxylase (TPH1), serotonin receptor 2C (HTR2C...... and sex. These new findings may aid the understanding of susceptibility to side effects such as weight gain during clinical antidepressive treatment....

  6. CYP2D6 and catechol-O-methyltransferase gene polymorphisms in Parkinson patients with levodopa-induced dyskinesias

    NARCIS (Netherlands)

    Ivanova, S.A.; Alifirova, V.M.; Pozhidaev, I.V.; Fedorenko, O.Y.; Osmanova, D.Z.; Tiguntsev, V.V.; Bokhan, N.A.; Zhukova, I.A.; Wilffert, B.; Loonen, A.J.M.

    2016-01-01

    Parkinson's disease (PD), a common neurodegenerative disorder caused by the loss of the dopaminergic input to the basal ganglia, is commonly treated with levodopa (L-DOPA). Use of this drug, however, is severely limited by the development of side effect. Levodopa-induced dyskinesias (LID) are

  7. Persistent pain after mastectomy with reconstruction.

    LENUS (Irish Health Repository)

    Hickey, Oonagh T

    2011-09-01

    To determine the prevalence of persistent postsurgical pain (PPSP) and its influence on functional status, and to examine associations between PPSP and single nucleotide polymorphisms of the catechol-O-methyltransferase (COMT) gene and the guanosine triphosphate cyclohydrolase 1 (GCH1) gene following mastectomy and reconstruction.

  8. Associations between genetic risk, functional brain network organization and neuroticism

    NARCIS (Netherlands)

    Servaas, Michelle N.; Geerligs, Linda; Bastiaansen, Jojanneke A.; Renken, Remco J.; Marsman, Jan-Bernard C.; Nolte, Ilja M.; Ormel, Johan; Aleman, Andre; Riese, Harriette

    2017-01-01

    Neuroticism and genetic variation in the serotonin-transporter (SLC6A4) and catechol-O-methyltransferase (COMT) gene are risk factors for psychopathology. Alterations in the functional integration and segregation of neural circuits have recently been found in individuals scoring higher on

  9. The TT genotype of the rs6860 polymorphism of the charged multivesicular body protein 1A gene is associated with susceptibility to fibromyalgia in southern Spanish women

    NARCIS (Netherlands)

    Estévez-López, Fernando; Aparicio, Virginia A; Ruiz, Jonatan R; Martínez-González, Luis J; Delgado-Fernández, Manuel; Álvarez-Cubero, María J

    In 2012, Barbosa et al. analysed the association between the genotype frequencies of the rs4680 and rs4818 polymorphisms of the catechol-O-methyltransferase (COMT) gene. Of note is that, in the abstract, they mentioned the rs6860 polymorphism when it should have been rs4680. Indeed, the rs6860

  10. Polymorphisms in Dopamine System Genes Are Associated with Individual Differences in Attention in Infancy

    Science.gov (United States)

    Holmboe, Karla; Nemoda, Zsofia; Fearon, R. M. Pasco; Csibra, Gergely; Sasvari-Szekely, Maria; Johnson, Mark H.

    2010-01-01

    Knowledge about the functional status of the frontal cortex in infancy is limited. This study investigated the effects of polymorphisms in four dopamine system genes on performance in a task developed to assess such functioning, the Freeze-Frame task, at 9 months of age. Polymorphisms in the catechol-O-methyltransferase ("COMT") and the…

  11. Catechol-O-methlytransferase inhibition alters pain and anxiety-related volitional behaviors through activation of β-adrenergic receptors in the rat

    Science.gov (United States)

    Kline, R. H.; Exposto, F. G.; O’Buckley, S. C.; Westlund, K. N.; Nackley, A. G.

    2015-01-01

    Reduced catechol-O-methyltransferase (COMT) activity resulting from genetic variation or pharmacological depletion results in enhanced pain perception in humans and nociceptive behaviors in animals. Using phasic mechanical and thermal reflex tests (e.g. von Frey, Hargreaves), recent studies show that acute COMT-dependent pain in rats is mediated by β-adrenergic receptors (βARs). In order to more closely mimic the characteristics of human chronic pain conditions associated with prolonged reductions in COMT, the present study sought to determine volitional pain-related and anxiety-like behavioral responses following sustained as well as acute COMT inhibition using an operant 10–45°C thermal place preference task and a light/dark preference test. In addition, we sought to evaluate the effects of sustained COMT inhibition on generalized body pain by measuring tactile sensory thresholds of the abdominal region. Results demonstrated that acute and sustained administration of the COMT inhibitor OR486 increased pain behavior in response to thermal heat. Further, sustained administration of OR486 increased anxiety behavior in response to bright light, as well as abdominal mechanosensation. Finally, all pain-related behaviors were blocked by the non-selective βAR antagonist propranolol. Collectively, these findings provide the first evidence that stimulation of ARs following acute or chronic COMT inhibition drives cognitive-affective behaviors associated with heightened pain that affects multiple body sites. PMID:25659347

  12. Lettres à Auguste Comte

    OpenAIRE

    Mill, John Stuart

    2016-01-01

    Ces lettres sont écrites en français et sont reproduites sans correction.   India Housele 13 juillet 1843Mon cher Monsieur Comte J’espère que cette lettre vous atteindra avant le commencement de votre tournée officielle, qui du reste ne suspendra pas sans doute notre correspondance, et je ne doute pas qu’à quelque temps d’ici je serai plus en état de vous écrire convenablement. Le dérangement passager que je vous ai annoncé dans ma dernière lettre, de ma santé morale et physique, ne s’est pas...

  13. Genetic Influences of OPRM1, OPRD1 and COMT on Morphine Analgesia in a Multi-Modal, Multi-Tissue Human Experimental Pain Model

    DEFF Research Database (Denmark)

    Nielsen, Lecia Møller; Christrup, Lona Louring; Sato, Hiroe

    2017-01-01

    (mechanical, electrical and thermal) and cold pressor test (immersion of the hand into ice water). Sixteen genetic polymorphisms of four candidate genes were explored. Variability in morphine analgesia to contact heat stimulation was associated with COMT rs4680 (P=0.04), and rectal thermal stimulation...

  14. 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

  15. 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.

  16. Biological and Mechanistic Characterization of Novel Prodrugs of Green Tea Polyphenol Epigallocatechin Gallate Analogs in Human Leiomyoma Cell Lines.

    Science.gov (United States)

    Ahmed, Reda Saber Ibrahim; Liu, Gang; Renzetti, Andrea; Farshi, Pershang; Yang, Huanjie; Soave, Claire; Saed, Ghassan; El-Ghoneimy, Ashraf Ahmed; El-Banna, Hossny Awad; Foldes, Robert; Chan, Tak-Hang; Dou, Q Ping

    2016-10-01

    Uterine fibroids (leiomyomas) are very common benign tumors grown on the smooth muscle layer of the uterus, present in up to 75% of reproductive-age women and causing significant morbidity in a subset of this population. Although the etiology and biology of uterine fibroids are unclear, strong evidence supports that cell proliferation, angiogenesis and fibrosis are involved in their formation and growth. Currently the only cure for uterine fibroids is hysterectomy; the available alternative therapies have limitations. Thus, there is an urgent need for developing a novel strategy for treating this condition. The green tea polyphenol epigallocatechin gallate (EGCG) inhibits the growth of uterine leiomyoma cells in vitro and in vivo, and the use of a green tea extract (containing 45% EGCG) has demonstrated clinical activity without side effects in women with symptomatic uterine fibroids. However, EGCG has a number of shortcomings, including low stability, poor bioavailability, and high metabolic transformations under physiological conditions, presenting challenges for its development as a therapeutic agent. We developed a prodrug of EGCG (Pro-EGCG or 1) which shows increased stability, bioavailability and biological activity in vivo as compared to EGCG. We also synthesized prodrugs of EGCG analogs, compounds 2a and 4a, in order to potentially reduce their susceptibility to methylation/inhibition by catechol-O-methyltransferase. Here, we determined the effect of EGCG, Pro-EGCG, and 2a and 4a on cultured human uterine leiomyoma cells, and found that 2a and 4a have potent antiproliferative, antiangiogenic, and antifibrotic activities. J. Cell. Biochem. 117: 2357-2369, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Improved radioenzymatic assay for plasma norepinephrine using purified phenylethanolamine n-methyltransferase

    International Nuclear Information System (INIS)

    Bowsher, R.R.; Henry, D.P.

    1986-01-01

    Radioenzymatic assays have been developed for catecholamines using either catechol O-methyltransferase (COMT) or phenylethanolamine N-methyltransferase (PNMT). Assays using PNMT are specific for norepinephrine (NE) and require minimal manipulative effort but until now have been less sensitive than the more complex procedures using COMT. The authors report an improved purification scheme for bovine PNMT which has permitted development of an NE assay with dramatically improved sensitivity (0.5 pg), specificity and reproducibility (C.V. < 5%). PNMT was purified by sequential pH 5.0 treatment and dialysis and by column chromatographic procedures using DEAE-Sephacel, Sepharcryl S-200 and Phenyl-Boronate Agarose. Recovery of PNMT through the purification scheme was 50%, while blank recovery was <.001%. NE can be directly quantified in 25 ul of human plasma and an 80 tube assay can be completed within 4 h. The capillary to venous plasma NE gradient was examined in 8 normotensive male subjects. Capillary plasma (NE (211.2 +/- 61.3 pg/ml)) was lower than venous plasma NE (366.6 +/- 92.5 pg/ml) in all subjects (p < 0.005). This difference suggests that capillary (NE) may be a unique indicator of sympathetic nervous system activity in vivo. In conclusion, purification of PNMT has facilitated development of an improved radioenzymatic for NE with significantly improved sensitivity

  18. Tolcapone suppresses ethanol intake in alcohol-preferring rats performing a novel cued access protocol.

    Science.gov (United States)

    McCane, Aqilah M; Czachowski, Cristine L; Lapish, Christopher C

    2014-09-01

    Dopamine (DA) has been shown to play a central role in regulating motivated behavior and encoding reward. Chronic drug abuse elicits a state of hypodopaminergia in the mesocorticolimbic (MCL) system in both humans and preclinical rodent models of addiction, including those modeling alcohol use disorders (AUD). Working under the hypothesis that reductions in the bioavailability of DA play an integral role in the expression of the excessive drinking phenotype, the catechol-O-methyltransferase (COMT) inhibitor tolcapone was used as a means to amplify cortical DA concentration and drinking behaviors were then assessed. Sucrose and ethanol (EtOH) consumption were measured in P and Wistar rats in both a free choice drinking protocol and a novel cued access protocol. Tolcapone attenuated the consumption of EtOH, and to a lesser extent sucrose, in P rats in the cued access protocol, while no effect was observed in the free choice drinking protocol. Tolcapone also decreased EtOH consumption in high drinking Wistar rats. A follow-up experiment using the indirect DA agonist d-amphetamine showed no change in EtOH consumption. Collectively, these data suggest that COMT inhibitors may be capable of alleviating the extremely motivating or salient nature of stimuli associated with alcohol. The hypothesis is put forth that the relative specificity of tolcapone for cortical DA systems may mediate the suppression of the high seeking/drinking phenotype. Copyright © 2014 by the Research Society on Alcoholism.

  19. Potential Moderators of Physical Activity on Brain Health

    Directory of Open Access Journals (Sweden)

    Regina L. Leckie

    2012-01-01

    Full Text Available Age-related cognitive decline is linked to numerous molecular, structural, and functional changes in the brain. However, physical activity is a promising method of reducing unfavorable age-related changes. Physical activity exerts its effects on the brain through many molecular pathways, some of which are regulated by genetic variants in humans. In this paper, we highlight genes including apolipoprotein E (APOE, brain derived neurotrophic factor (BDNF, and catechol-O-methyltransferase (COMT along with dietary omega-3 fatty acid, docosahexaenoic acid (DHA, as potential moderators of the effect of physical activity on brain health. There are a growing number of studies indicating that physical activity might mitigate the genetic risks for disease and brain dysfunction and that the combination of greater amounts of DHA intake with physical activity might promote better brain function than either treatment alone. Understanding whether genes or other lifestyles moderate the effects of physical activity on neurocognitive health is necessary for delineating the pathways by which brain health can be enhanced and for grasping the individual variation in the effectiveness of physical activity interventions on the brain and cognition. There is a need for future research to continue to assess the factors that moderate the effects of physical activity on neurocognitive function.

  20. Hierarchical prediction errors in midbrain and septum during social learning.

    Science.gov (United States)

    Diaconescu, Andreea O; Mathys, Christoph; Weber, Lilian A E; Kasper, Lars; Mauer, Jan; Stephan, Klaas E

    2017-04-01

    Social learning is fundamental to human interactions, yet its computational and physiological mechanisms are not well understood. One prominent open question concerns the role of neuromodulatory transmitters. We combined fMRI, computational modelling and genetics to address this question in two separate samples (N = 35, N = 47). Participants played a game requiring inference on an adviser's intentions whose motivation to help or mislead changed over time. Our analyses suggest that hierarchically structured belief updates about current advice validity and the adviser's trustworthiness, respectively, depend on different neuromodulatory systems. Low-level prediction errors (PEs) about advice accuracy not only activated regions known to support 'theory of mind', but also the dopaminergic midbrain. Furthermore, PE responses in ventral striatum were influenced by the Met/Val polymorphism of the Catechol-O-Methyltransferase (COMT) gene. By contrast, high-level PEs ('expected uncertainty') about the adviser's fidelity activated the cholinergic septum. These findings, replicated in both samples, have important implications: They suggest that social learning rests on hierarchically related PEs encoded by midbrain and septum activity, respectively, in the same manner as other forms of learning under volatility. Furthermore, these hierarchical PEs may be broadcast by dopaminergic and cholinergic projections to induce plasticity specifically in cortical areas known to represent beliefs about others. © The Author (2017). Published by Oxford University Press.

  1. Psychiatric and cognitive symptoms in Huntington's disease are modified by polymorphisms in catecholamine regulating enzyme genes

    DEFF Research Database (Denmark)

    Vinther-Jensen, T; Nielsen, Troels Tolstrup; Budtz-Jørgensen, E

    2016-01-01

    Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder characterized by motor, psychiatric, and cognitive manifestations. HD is caused by a CAG repeat expansion in the Huntingtin (HTT) gene but the exact pathogenesis remains unknown. Dopamine imbalance has......-described cohort of Danish HD gene-expansion carriers. We show that cognitive impairment and psychiatric symptoms in HD are modified by polymorphisms in the monoamine oxidase A (MAOA) and catechol-O-methyltransferase (COMT) genes and by the 4p16.3 B haplotype. These results support the theory of dopamine imbalance...

  2. Dopamine in human follicular fluid is associated with cellular uptake and metabolism-dependent generation of reactive oxygen species in granulosa cells: implications for physiology and pathology.

    Science.gov (United States)

    Saller, S; Kunz, L; Berg, D; Berg, U; Lara, H; Urra, J; Hecht, S; Pavlik, R; Thaler, C J; Mayerhofer, A

    2014-03-01

    Is the neurotransmitter dopamine (DA) in the human ovary involved in the generation of reactive oxygen species (ROS)? Human ovarian follicular fluid contains DA, which causes the generation of ROS in cultured human granulosa cells (GCs), and alterations of DA levels in follicular fluid and DA uptake/metabolism in GCs in patients with polycystic ovary syndrome (PCOS) are linked to increased levels of ROS. DA is an important neurotransmitter in the brain, and the metabolism of DA results in the generation of ROS. DA was detected in human ovarian homogenates, but whether it is present in follicular fluid and plays a role in the follicle is not known. We used human follicular fluid from patients undergoing in vitro fertilization (IVF), GCs from patients with or without PCOS and also employed mathematical modeling to investigate the presence of DA and its effects on ROS. DA in follicular fluid and GCs was determined by enzyme-linked immunosorbent assay. GC viability, apoptosis and generation of ROS were monitored in GCs upon addition of DA. Inhibitors of DA uptake and metabolism, an antioxidant and DA receptor agonists, were used to study cellular uptake and the mechanism of DA-induced ROS generation. Human GCs were examined for the presence and abundance of transcripts of the DA transporter (DAT; SLC6A3), the DA-metabolizing enzymes monoamine oxidases A/B (MAO-A/B) and catechol-O-methyltransferase and the vesicular monoamine transporter. A computational model was developed to describe and predict DA-induced ROS generation in human GCs. We found DA in follicular fluid of ovulatory follicles of the human ovary and in GCs. DAT and MAO-A/B, which are expressed by GCs, are prerequisites for a DA receptor-independent generation of ROS in GCs. Blockers of DAT and MAO-A/B, as well as an antioxidant, prevented the generation of ROS (P human follicular compartment, functions of DA could only be studied in IVF-derived GCs, which can be viewed as a cellular model for the

  3. Distinct effects of ketamine and acetyl l-carnitine on the dopamine system in zebrafish

    Science.gov (United States)

    Robinson, Bonnie L.; Dumas, Melanie; Cuevas, Elvis; Gu, Qiang; Paule, Merle G.; Ali, Syed F.; Kanungo, Jyotshna

    2016-01-01

    Ketamine, a noncompetitive N-methyl-d-aspartic acid (NMDA) receptor antagonist is commonly used as a pediatric anesthetic. We have previously shown that acetyl L-carnitine (ALCAR) prevents ketamine toxicity in zebrafish embryos. In mammals, ketamine is known to modulate the dopaminergic system. NMDA receptor antagonists are considered as promising anti-depressants, but the exact mechanism of their function is unclear. Here, we measured the levels of dopamine (DA) and its metabolites, 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the zebrafish embryos exposed to ketamine in the presence and absence of 0.5 mM ALCAR. Ketamine, at lower doses (0.1–0.3 mM), did not produce significant changes in DA, DOPAC or HVA levels in 52 h post-fertilization embryos treated for 24 h. In these embryos, tyrosine hydroxylase (TH) mRNA expression remained unchanged. However, 2 mM ketamine (internal embryo exposure levels equivalent to human anesthetic plasma concentration) significantly reduced DA level and TH mRNA indicating that DA synthesis was adversely affected. In the presence or absence of 2 mM ketamine, ALCAR showed similar effects on DA level and TH mRNA, but increased DOPAC level compared to control. ALCAR reversed 2 mM ketamine-induced reduction in HVA levels. With ALCAR alone, the expression of genes encoding the DA metabolizing enzymes, MAO (monoamine oxidase) and catechol-O-methyltransferase (COMT), was not affected. However, ketamine altered MAO mRNA expression, except at the 0.1 mM dose. COMT transcripts were reduced in the 2 mM ketamine-treated group. These distinct effects of ketamine and ALCAR on the DA system may shed some light on the mechanism on how ketamine can work as an anti-depressant, especially at sub-anesthetic doses that do not affect DA metabolism and suppress MAO gene expression. PMID:26898327

  4. The Development of Cognitive Control in Children with Chromosome 22q11.2 Deletion Syndrome

    Directory of Open Access Journals (Sweden)

    Heather M Shapiro

    2014-06-01

    Full Text Available Chromosome 22q11.2 Deletion Syndrome (22q11.2DS is caused by the most common human microdeletion, and it is associated with cognitive impairments across many domains. While impairments in cognitive control have been described in children with 22q11.2DS, the nature and development of these impairments are not clear. Children with 22q11.2DS and typically developing children (TD were tested on four well-validated tasks aimed at measuring specific foundational components of cognitive control: response inhibition, cognitive flexibility, and working memory. Molecular assays were also conducted in order to examine genotype of catechol-O-methyltransferase (COMT, a gene located within the deleted region in 22q11.2DS and hypothesized to play a role in cognitive control. Mixed model regression analyses were used to examine group differences, as well as age-related effects on cognitive control component processes in a cross-sectional analysis. Regression models with COMT genotype were also conducted in order to examine potential effects of the different variants of the gene. Response inhibition, cognitive flexibility, and working memory were impaired in children with 22q11.2DS relative to TD children, even after accounting for global intellectual functioning (as measured by full-scale IQ. When compared with TD individuals, children with 22q11.2DS demonstrated atypical age-related patterns of response inhibition and cognitive flexibility. Both groups demonstrated typical age-related associations with working memory. The results of this cross-sectional analysis suggest a specific aberration in the development of systems mediating response inhibition in a sub-set of children with 22q11.2DS. It will be important to follow up with longitudinal analyses to directly examine these developmental trajectories, and correlate neurocognitive variables with clinical and adaptive outcome measures.

  5. External and internal standards in the single-isotope derivative (radioenzymatic) measurement of plasma norepinephrine and epinephrine

    International Nuclear Information System (INIS)

    Shah, S.D.; Clutter, W.E.; Cryer, P.E.

    1985-01-01

    In plasma from normal humans (n = 9, 35 samples) and from patients with diabetes mellitus (n = 12, 24 samples) single-isotope derivative (radioenzymatic) plasma norepinephrine and epinephrine concentrations calculated from external standard curves constructed in a normal plasma pool were identical to those calculated from internal standards added to an aliquot of each plasma sample. In plasma from patients with end-stage renal failure receiving long-term dialysis (n = 34, 109 samples), competitive catechol-O-methyltransferase (COMT) inhibitory activity resulted in a systematic error when external standards in a normal plasma pool were used, as reported previously; values so calculated averaged 21% (+/- 12%, SD) lower than those calculated from internal standards. However, when external standard curves were constructed in plasma from a given patient with renal failure and used to calculate that patient's values, or in a renal failure plasma pool and used to calculate all renal failure values, norepinephrine and epinephrine concentrations were not significantly different from those calculated from internal standards. We conclude: (1) External standard curves constructed in plasma from a given patient with renal failure can be used to measure norepinephrine and epinephrine in plasma from that patient; further, external standards in a renal failure plasma pool can be used for assays in patients with end-stage renal failure receiving long-term dialysis. (2) Major COMT inhibitory activity is not present commonly if samples from patients with renal failure are excluded. Thus, it would appear that external standard curves constructed in normal plasma can be used to measure norepinephrine and epinephrine precisely in samples from persons who do not have renal failure

  6. Le Comte de Monte Cristo: da literatura ao cinema

    OpenAIRE

    Caravela, Natércia Murta Silva

    2008-01-01

    A presente dissertação discute o diálogo estabelecido entre literatura e cinema no tratamento da personagem principal – um homem traído que se vinga de forma cruel dos seus inimigos – na obra literária Le Comte de Monte-Cristo, de Alexandre Dumas, e nas três adaptações fílmicas escolhidas: Le Comte de Monte-Cristo de Robert Vernay (1943); The count of Monte Cristo de David Greene (1975) e The count of Monte Cristo de Kevin Reynolds (2002). O projecto centra-se na análise da ...

  7. Influence of BDNF and COMT polymorphisms on emotional decision making.

    Science.gov (United States)

    Kang, Jee In; Namkoong, Kee; Ha, Ra Yeon; Jhung, Kyungun; Kim, Yang Tae; Kim, Se Joo

    2010-06-01

    Decision making is an important brain function. Although little is known about the genetic basis of decision making, it has been suggested that it is mediated by the modulation of neurotransmitter systems. We investigated how the BDNF Val66Met and COMT Val158Met polymorphisms affect emotional decision making using the Iowa Gambling Task (IGT). One hundred sixty-eight healthy Korean college students (93 males, 75 females) with a complete dataset were included in the data analysis. The IGT and genotyping for the polymorphisms of BDNF Val66Met and COMT Val158Met were performed. Both Met/Met and Val/Met of the BDNF Val66Met polymorphism were significantly associated with a lower mean score of blocks 3-5 of the IGT and with less improvement from block 1 to block 3-5 than the Val/Val. However, the BDNF was not significantly associated with the score of block 1, and the COMT Val158Met polymorphism produced no significant effect on IGT performance. No interaction effect was observed between the BDNF and the COMT for the IGT. These findings suggest the BDNF Val66Met may affect the emotional decision making performance. (c) 2010 Elsevier Ltd. All rights reserved.

  8. COMT (Val158Met and BDNF (Val66Met Genes Polymorphism in Schizophrenia: A Case-Control Report

    Directory of Open Access Journals (Sweden)

    ramin saravani

    2017-10-01

    Full Text Available Objective: The effects of human brain-derived neurotropic factor (BDNF Val66Met (G>A and the human Catechol-O-methylTransferase (COMT Val158Met (G>A polymorphisms on Schizophrenia (SCZ risk were evaluated.Methods: This case control study included 92 SCZ patients and 92 healthy controls (HCs. Genotyping of both variants were conducted using Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR.Results: The findings showed that BDNF Val66Met (G>A variant increased the risk of SCZ (OR=2.008 95%CI=1.008-4.00, P=0.047, GA vs. GG, OR=3.876 95%CI=1.001-14.925, P=0.049. AA vs. GG, OR=2.272. 95%CI=1.204-4.347, P=0.011, GA+AA vs. GG, OR=2.22 95%CI=1.29-3.82. P=0.005, A vs. G. COMT Val158Met (G>A polymorphism was not associated with the risk/protective of SCZ.Conclusion: The results proposed that BDNF Val66Met (G>A polymorphism may increase the risk of SCZ development and did not support an association between COMT Val158Met (G>A variant and risk/protective of SCZ. Further studies and different ethnicities are recommended to confirm the findings.

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

    Science.gov (United States)

    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.

  10. Pharmacokinetics of opicapone, a third-generation COMT inhibitor, after single and multiple oral administration: A comparative study in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Gonçalves, Daniela [Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra (Portugal); CNC – Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra (Portugal); Alves, Gilberto, E-mail: gilberto@fcsaude.ubi.pt [CNC – Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra (Portugal); CICS-UBI – Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã (Portugal); Fortuna, Ana [Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra (Portugal); CNC – Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra (Portugal); Soares-da-Silva, Patrício [Department of Research and Development, BIAL – Portela & Ca S.A., Av. da Siderurgia Nacional, 4745-457 S. Mamede do Coronado (Portugal); MedInUP – Center for Drug Discovery and Innovative Medicines, University Porto, Porto (Portugal); Falcão, Amílcar [Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra (Portugal); CNC – Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra (Portugal)

    2017-05-15

    Opicapone is a novel potent, reversible and purely peripheral catechol-O-methyltransferase inhibitor that has been developed to be used as an adjunct to levodopa/aromatic L-amino acid decarboxylase inhibitor therapy for Parkinson's disease. Thus, this study aimed to compare the plasma pharmacokinetics of opicapone and its active metabolite (BIA 9-1079) after the administration of single and multiple oral doses to rats. Wistar rats (n = 8 per group) were orally treated with single (30, 60 or 90 mg/kg) or multiple (30 mg/kg once-daily for seven consecutive days) oral doses of opicapone. Blood samples were collected up to 24 h post-dosing through a cannula introduced in the tail vein of rats. After quantifying opicapone and BIA 9-1079 in plasma, a non-compartmental pharmacokinetic analysis was performed. Opicapone was quickly absorbed (time to reach the maximum plasma concentration ≤ 2 h) in both dosage regimens and the extent of systemic exposure to opicapone increased approximately in a dose-proportional manner after single-dosing within the studied dose range (30–90 mg/kg). Opicapone and BIA 9-1079 showed a relatively short plasma elimination half-life (1.58–4.50 h) and a small systemic accumulation after multiple-dosing. Hence, no pharmacokinetic concerns are expected when opicapone is administered with a once-daily dosing regimen. - Highlights: • Opicapone is relatively rapid absorbed after oral administration to rats. • Systemic exposure to opicapone increases approximately in a dose-proportional manner. • Opicapone and BIA 9-1079 show a small systemic accumulation after multiple-dosing.

  11. Effect of entacapone on colon motility and ion transport in a rat model of Parkinson’s disease

    Science.gov (United States)

    Li, Li-Sheng; Liu, Chen-Zhe; Xu, Jing-Dong; Zheng, Li-Fei; Feng, Xiao-Yan; Zhang, Yue; Zhu, Jin-Xia

    2015-01-01

    AIM: To study the effects of entacapone, a catechol-O-methyltransferase inhibitor, on colon motility and electrolyte transport in Parkinson’s disease (PD) rats. METHODS: Distribution and expression of catechol-O-methyltransferase (COMT) were measured by immunohistochemistry and Western blotting methods. The colonic smooth muscle motility was examined in vitro by means of a muscle motility recording device. The mucosal electrolyte transport of PD rats was examined by using a short-circuit current (ISC) technique and scanning ion-selective electrode technique (SIET). Intracellular detection of cAMP and cGMP was accomplished by radioimmunoassay testing. RESULTS: COMT was expressed in the colons of both normal and PD rats, mainly on the apical membranes of villi and crypts in the colon. Compared to normal controls, PD rats expressed less COMT. The COMT inhibitor entacapone inhibited contraction of the PD rat longitudinal muscle in a dose-dependent manner. The β2 adrenoceptor antagonist ICI-118,551 blocked this inhibitory effect by approximately 67% (P fluid, as well as pretreatment using adenylate cyclase inhibitor MDL12330A. As an inhibitor of prostaglandin synthetase, indomethacin can inhibit entacapone-induced ISC by 45% (P < 0.01). When SIET was applied to measure Cl- flux changes, this provided similar results. Entacapone significantly increased intracellular cAMP content in the colonic mucosa, which was greatly inhibited by indomethacin. CONCLUSION: COMT expression exists in rat colons. The β2 adrenoceptor is involved in the entacapone-induced inhibition of colon motility. Entacapone induces cAMP-dependent Cl- secretion in the PD rat. PMID:25834315

  12. Analgesia and Opioids: A Pharmacogenetics Shortlist for Implementation in Clinical Practice.

    Science.gov (United States)

    Matic, Maja; de Wildt, Saskia N; Tibboel, Dick; van Schaik, Ron H N

    2017-07-01

    The use of opioids to alleviate pain is complicated by the risk of severe adverse events and the large variability in dose requirements. Pharmacogenetics (PGx) could possibly be used to tailor pain medication based on an individual's genetic background. Many potential genetic markers have been described, and the importance of genetic predisposition in opioid efficacy and toxicity has been demonstrated in knockout mouse models and human twin studies. Such predictors are especially of value for neonates and young children, in whom the assessment of efficacy or side effects is complicated by the inability of the patient to communicate this properly. The current problem is determining which of the many potential candidates to focus on for clinical implementation. We systematically searched publications on PGx for opioids in 5 databases, aiming to identify PGx markers with sufficient robust data and high enough occurrence for potential clinical application. The initial search yielded 4257 unique citations, eventually resulting in 852 relevant articles covering 24 genes. From these genes, we evaluated the evidence and selected the most promising 10 markers: cytochrome P450 family 2 subfamily D member 6 ( CYP2D6 ), cytochrome P450 family 3 subfamily A member 4 ( CYP3A4 ), cytochrome P450 family 3 subfamily A member 5 ( CYP3A5 ), UDP glucuronosyltransferase family 2 member B7 ( UGT2B7 ), ATP binding cassette subfamily B member 1 ( ABCB1 ), ATP binding cassette subfamily C member 3 ( ABCC3 ), solute carrier family 22 member 1 ( SLC22A1 ), opioid receptor kappa 1 ( OPRM1 ), catechol- O -methyltransferase ( COMT ), and potassium voltage-gated channel subfamily J member 6 ( KCNJ6 ). Treatment guidelines based on genotype are already available only for CYP2D6 . The application of PGx in the management of pain with opioids has the potential to improve therapy. We provide a shortlist of 10 genes that are the most promising markers for clinical use in this context. © 2016

  13. 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.

  14. estimation of the sanitary impact associated to the domestic exposure to radon in Franche-Comte

    International Nuclear Information System (INIS)

    Catelinois, O.; Pirard, P.; Clinard, F.; Aury, K.; Tillier, C.; Aury, K.; Noury, L.; Hochard, A.

    2008-01-01

    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.)

  15. Gender effects of the COMT Val 158 Met genotype on verbal fluency in healthy adults.

    Science.gov (United States)

    Soeiro-De-Souza, Marcio Gerhardt; Bio, Danielle Soares; David, Denise Petresco; Missio, Giovani; Lima, Bruno; Fernandes, Fernando; Machado-Vieira, Rodrigo; Moreno, Ricardo Alberto

    2013-09-01

    Cognitive performance in healthy individuals is associated with gender differences in specific tests; a female advantage has been demonstrated in language tests, whereas a male advantage has been demonstrated in spatial relation examinations. The prefrontal cortex (PFC) mediates important cognitive domains and is influenced by dopamine (DA) activity. The single nucleotide polymorphism (SNP) rs4680 in the catechol‑O‑methyltransferase (COMT) gene results in an amino acid substitution from valine (Val) to methionine (Met). The Met allele has been demonstrated to decrease COMT enzyme activity and improve PFC cognitive function. COMT regulates DA activity in the PFC and exhibits gender effects. The aim of the present study was to investigate the gender‑specific effects of the COMT genotype on cognition in healthy young adults. Seventy‑six healthy subjects were genotyped for COMT rs4680 and submitted to an extensive range of neuropsychological tests assessing aspects of PFC function. The COMT Met allele influenced the performance of executive function. The results revealed gender effects of the COMT rs4680 Met allele on verbal fluency, with positive effects in males and negative effects in females. This suggested that DA activity affects cognitive function in different ways, according to gender.

  16. COMT val108/158 met genotype affects neural but not cognitive processing in healthy individuals.

    Science.gov (United States)

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

    2010-03-01

    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.

  17. Association of functional variations in COMT and GCH1 genes with postherniotomy pain and related impairment

    DEFF Research Database (Denmark)

    Belfer, Inna; Dai, Feng; Kehlet, Henrik

    2015-01-01

    Persistent postoperative pain is a well-established clinical problem with potential severe personal and socioeconomic implications. The prevalence of persistent pain varies across surgery types. Severe persistent pain and related impairment occur in 5% to 10% of patients after groin hernia repair....... The substantial interindividual variability in pain-related phenotypes within each surgery type cannot be explained by environmental factors alone, suggesting that genetic variation may play a role. We investigated the contribution of COMT and GCH1 to persistent postherniotomy pain (PPP)-related functional...... moderate-to-severe pain-related activity impairment 6 months postoperatively as measured by Activity Assessment Scale (≥8.3). Patients with the G allele of COMT SNP rs6269 and C allele of COMT SNP rs4633 had less impairment (P = 0.03 and 0.01, respectively); in addition, the COMT haplotype GCG...

  18. Modulation of Estrogen Chemical Carcinogenesis by Botanical Supplements used for Postmenopausal Women’s Health

    Science.gov (United States)

    Snelten, Courtney S.; Dietz, Birgit; Bolton, Judy L.

    2012-01-01

    Breast cancer risk has been associated with long-term estrogen exposure including traditional hormone therapy (HT, formally hormone replacement therapy). To avoid traditional HT and associated risks, women have been turning to botanical supplements such as black cohosh, red clover, licorice, hops, dong gui, and ginger to relieve menopausal symptoms despite a lack of efficacy evidence. The mechanisms of estrogen carcinogenesis involve both hormonal and chemical pathways. Botanical supplements could protect women from estrogen carcinogenesis by modulating key enzymatic steps [aromatase, P4501B1, P4501A1, catechol-O-methyltransferase (COMT), NAD(P)H quinone oxidoreductase 1 (NQO1), and reactive oxygen species (ROS) scavenging] in estradiol metabolism leading to estrogen carcinogenesis as outlined in Figure 1. This review summarizes the influence of popular botanical supplements used for women’s health on these key steps in the estrogen chemical carcinogenesis pathway, and suggests that botanical supplements may have added chemopreventive benefits by modulating estrogen metabolism. PMID:24223609

  19. Association Between Genetic Polymorphisms and Pain Sensitivity in Patients with Hip Osteoarthritis

    DEFF Research Database (Denmark)

    Olesen, Anne E; Nielsen, Lecia M; Feddersen, Søren

    2018-01-01

    , kappa, and delta opioid receptor genes (OPRM1, OPRK1, and OPRD1) and the catechol-O-methyltransferase gene (COMT) influenced the pain phenotype in patients with osteoarthritis. METHODS: The frequencies of 17 polymorphisms were examined. Pain sensitivity was assessed preoperatively by (1) hip rotation......BACKGROUND: Factors such as age, gender, and genetic polymorphisms may explain individual differences in pain phenotype. Genetic associations with pain sensitivity have previously been investigated in osteoarthritis patients, with a focus on the P2X7, TRPV1, and TACR1 genes. However, other genes...... may play a role as well. Osteoarthritis is a common joint disease, and many patients suffering from this disease are thought to have increased sensitivity to noxious stimuli resulting from sensitization in the nociceptive system. The aim of this study was to investigate if genetic variants of mu...

  20. Sequential processing deficits in schizophrenia: relationship to neuropsychology and genetics.

    Science.gov (United States)

    Hill, S Kristian; Bjorkquist, Olivia; Carrathers, Tarra; Roseberry, Jarett E; Hochberger, William C; Bishop, Jeffrey R

    2013-12-01

    Utilizing a combination of neuropsychological and cognitive neuroscience approaches may be essential for characterizing cognitive deficits in schizophrenia and eventually assessing cognitive outcomes. This study was designed to compare the stability of select exemplars for these approaches and their correlations in schizophrenia patients with stable treatment and clinical profiles. Reliability estimates for serial order processing were comparable to neuropsychological measures and indicate that experimental serial order processing measures may be less susceptible to practice effects than traditional neuropsychological measures. Correlations were moderate and consistent with a global cognitive factor. Exploratory analyses indicated a potentially critical role of the Met allele of the Catechol-O-methyltransferase (COMT) Val158Met polymorphism in externally paced sequential recall. Experimental measures of serial order processing may reflect frontostriatal dysfunction and be a useful supplement to large neuropsychological batteries. © 2013.

  1. Methylenetetrahydrofolate reductase deficiency alters levels of glutamate and γ-aminobutyric acid in brain tissue

    Directory of Open Access Journals (Sweden)

    N.M. Jadavji

    2015-06-01

    Full Text Available Methylenetetrahydrofolate reductase (MTHFR is an enzyme key regulator in folate metabolism. Deficiencies in MTHFR result in increased levels of homocysteine, which leads to reduced levels of S-adenosylmethionine (SAM. In the brain, SAM donates methyl groups to catechol-O-methyltransferase (COMT, which is involved in neurotransmitter analysis. Using the MTHFR-deficient mouse model the purpose of this study was to investigate levels of monoamine neurotransmitters and amino acid levels in brain tissue. MTHFR deficiency affected levels of both glutamate and γ-aminobutyric acid in within the cerebellum and hippocampus. Mthfr−/− mice had reduced levels of glutamate in the amygdala and γ-aminobutyric acid in the thalamus. The excitatory mechanisms of homocysteine through activation of the N-methyl-d-aspartate receptor in brain tissue might alter levels of glutamate and γ-aminobutyric acid.

  2. Age-related decline in brain resources modulates genetic effects on cognitive functioning

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    Ulman Lindenberger

    2008-12-01

    Full Text Available Individual differences in cognitive performance increase from early to late adulthood, likely reflecting influences of a multitude of factors. We hypothesize that losses in neurochemical and anatomical brain resources in normal aging modulate the effects of common genetic variations on cognitive functioning. Our hypothesis is based on the assumption that the function relating brain resources to cognition is nonlinear, so that genetic differences exert increasingly large effects on cognition as resources recede from high to medium levels in the course of aging.Direct empirical support for this hypothesis comes from a study by Nagel et al. (2008, who reported that the effects of the Catechol-O-Methyltransferase (COMT gene on cognitive performance are magnified in old age and interacted with the Brain-Derived Neurotrophic Factor (BDNF gene. We conclude that common genetic polymorphisms contribute to the increasing heterogeneity of cognitive functioning in old age. Extensions of the hypothesis to other polymorphisms are discussed.

  3. The effect of the COMT val(158)met polymorphism on neural correlates of semantic verbal fluency.

    Science.gov (United States)

    Krug, Axel; Markov, Valentin; Sheldrick, Abigail; Krach, Sören; Jansen, Andreas; Zerres, Klaus; Eggermann, Thomas; Stöcker, Tony; Shah, N Jon; Kircher, Tilo

    2009-12-01

    Variation in the val(158)met polymorphism of the COMT gene has been found to be associated with cognitive performance. In functional neuroimaging studies, this dysfunction has been linked to signal changes in prefrontal areas. Given the complex modulation and functional heterogeneity of frontal lobe systems, further specification of COMT gene-related phenotypes differing in prefrontally mediated cognitive performance are of major interest. Eighty healthy individuals (54 men, 26 women; mean age 23.3 years) performed an overt semantic verbal fluency task while brain activation was measured with functional magnetic resonance imaging (fMRI). COMT val(158)met genotype was determined and correlated with brain activation measured with fMRI during the task. Although there were no differences in performance, brain activation in the left inferior frontal gyrus [Brodmann area 10] was positively correlated with the number of val alleles in the COMT gene. COMT val(158)met status modulates brain activation during the language production on a semantic level in an area related to executive functions.

  4. 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.

  5. 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.

  6. Simultaneous Downregulation of MTHFR and COMT in Switchgrass Affects Plant Performance and Induces Lesion-Mimic Cell Death

    Directory of Open Access Journals (Sweden)

    Sijia Liu

    2017-06-01

    Full Text Available Switchgrass (Panicum virgatum has been developed into a model lignocellulosic bioenergy crop. Downregulation of caffeic acid O-methyltransferase (COMT, a key enzyme in lignin biosynthesis, has been shown to alter lignification and increase biofuel yield in switchgrass. Methylenetetrahydrofolate reductase (MTHFR mediates C1 metabolism and provides methyl units consumed by COMT. It was predicted that co-silencing of MTHFR and COMT would impact lignification even more than either of the single genes. However, our results showed that strong downregulation of MTHFR in a COMT-deficient background led to altered plant growth and development, but no significant change in lignin content or composition was found when compared with COMT plants. Another unexpected finding was that the double MTHFR/COMT downregulated plants showed a novel lesion-mimic leaf phenotype. Molecular analyses revealed that the lesion-mimic phenotype was caused by the synergistic effect of MTHFR and COMT genes, with MTHFR playing a predominant role. Microarray analysis showed significant induction of genes related to oxidative and defense responses. The results demonstrated the lack of additive effects of MTHFR and COMT on lignification. Furthermore, this research revealed an unexpected role of the two genes in the modulation of lesion-mimic cell death as well as their synergistic effects on agronomic performance.

  7. MB-COMT promoter DNA methylation is associated with working-memory processing in schizophrenia patients and healthy controls

    NARCIS (Netherlands)

    E. Walton (Esther); J. Liu (Jingyu); J. Hass (Johanna); T.J.H. White (Tonya); M. Scholz (Markus); V. Rœssner (Veit); R.L. Gollub (Randy); V.D. Calhoun (Vince); S.M. Ehrlich (Stefan)

    2014-01-01

    textabstractMany genetic studies report mixed results both for the associations between COMT polymorphisms and schizophrenia and for the effects of COMT variants on common intermediate phenotypes of the disorder. Reasons for this may include small genetic effect sizes and the modulation of

  8. Simultaneous Downregulation of MTHFR and COMT in Switchgrass Affects Plant Performance and Induces Lesion-Mimic Cell Death.

    Science.gov (United States)

    Liu, Sijia; Fu, Chunxiang; Gou, Jiqing; Sun, Liang; Huhman, David; Zhang, Yunwei; Wang, Zeng-Yu

    2017-01-01

    Switchgrass ( Panicum virgatum ) has been developed into a model lignocellulosic bioenergy crop. Downregulation of caffeic acid O -methyltransferase (COMT), a key enzyme in lignin biosynthesis, has been shown to alter lignification and increase biofuel yield in switchgrass. Methylenetetrahydrofolate reductase (MTHFR) mediates C1 metabolism and provides methyl units consumed by COMT. It was predicted that co-silencing of MTHFR and COMT would impact lignification even more than either of the single genes. However, our results showed that strong downregulation of MTHFR in a COMT -deficient background led to altered plant growth and development, but no significant change in lignin content or composition was found when compared with COMT plants. Another unexpected finding was that the double MTHFR/COMT downregulated plants showed a novel lesion-mimic leaf phenotype. Molecular analyses revealed that the lesion-mimic phenotype was caused by the synergistic effect of MTHFR and COMT genes, with MTHFR playing a predominant role. Microarray analysis showed significant induction of genes related to oxidative and defense responses. The results demonstrated the lack of additive effects of MTHFR and COMT on lignification. Furthermore, this research revealed an unexpected role of the two genes in the modulation of lesion-mimic cell death as well as their synergistic effects on agronomic performance.

  9. Structural Characterization of Lignin in Wild-Type versus COMT Down-Regulated Switchgrass

    Energy Technology Data Exchange (ETDEWEB)

    Samuel, Reichel [School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA (United States); BioEnergy Science Center, Oak Ridge, TN (United States); Pu, Yunqiao, E-mail: yunqiao.pu@ipst.gatech.edu [BioEnergy Science Center, Oak Ridge, TN (United States); Institute of Paper Science and Technology, Georgia Institute of Technology, Atlanta, GA (United States); Jiang, Nan [School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA (United States); BioEnergy Science Center, Oak Ridge, TN (United States); Fu, Chunxiang [Forage Improvement Division, The Samuel Roberts Noble Foundation, Ardmore, OK (United States); Wang, Zeng-Yu [BioEnergy Science Center, Oak Ridge, TN (United States); Forage Improvement Division, The Samuel Roberts Noble Foundation, Ardmore, OK (United States); Ragauskas, Arthur, E-mail: yunqiao.pu@ipst.gatech.edu [School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA (United States); BioEnergy Science Center, Oak Ridge, TN (United States)

    2014-01-20

    This study examined the chemical structural characteristics of cellulolytic enzyme lignin isolated from switchgrass focusing on comparisons between wild-type control and caffeic acid 3-O-methyltransferase (COMT) down-regulated transgenic line. Nuclear magnetic resonance techniques including {sup 13}C, {sup 31}P, and two-dimensional {sup 13}C-{sup 1}H heteronuclear single quantum coherence as well as gel permeation chromatography were employed. Compared to the wild-type, the COMT down-regulated transgenic switchgrass lignin demonstrated a decrease in syringyl (S):guaiacyl (G) ratio and p-coumarate:ferulate ratio, an increase in relative abundance of phenylcoumaran unit, and a comparable content of total free phenolic OH groups along with formation of benzodioxane unit. In addition, COMT down-regulation had no significant effects on the lignin molecular weights during its biosynthesis process.

  10. 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

  11. Epistatic Interaction of CYP1A1 and COMT Polymorphisms in Cervical Cancer

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    Andreia Matos

    2016-01-01

    Full Text Available There is a clear association between the excessive and cumulative exposure to estrogens and the development of cancer in hormone-sensitive tissues, such as the cervix. We studied the association of CYP1A1 M1 (rs4646903 and COMT (rs4680 polymorphisms in 130 cervical cancer cases (c-cancer and 179 controls. The CYP1A1 TT genotype was associated with a lower risk for c-cancer (OR = 0.39, p=0.002. The allele C of CYP1A1 was a risk for c-cancer (OR = 2.29, p=0.002. Women with COMT LL genotype had a higher risk of developing c-cancer (OR = 4.83, p<0.001. For the interaction of the CYP1A1&COMT, we observed that TC&HL genotypes had a greater risk for c-cancer (OR = 6.07, p=0.006 and TT&HL genotypes had a protection effect (OR = 0.24, p<0.001. The CYP1A1 TT and COMT LL genotypes had higher estradiol levels in c-cancer (p<0.001 and p=0.037, resp.. C-cancer is associated with less production of 2-methoxy-estradiol resultant of functional polymorphisms of CYP1A1 and COMT, separately. CYP1A1 and COMT work in a metabolic sequence and their interaction could lead to an alternative pathway of estrogen metabolism with production of 16-OH-estrone that is more proliferative.

  12. Association of the 3′ Region of COMT with Schizophrenia in Taiwan

    Directory of Open Access Journals (Sweden)

    Yi-Ling Chien

    2009-04-01

    Conclusion: The SNP rs165599, which has been mapped to the 3′-UTR region of the COMT gene, was significantly associated with schizophrenia in our family study, and possibly associated with the age of onset, delusion/hallucination symptom dimension, and CPT performance. Therefore, COMT may contribute to the genetic risk for schizophrenia not through the Val108/158 Met polymorphism, but through other variants that are situated 3′ to this region, in the Taiwanese population. Nevertheless, the true associated functional variants in our subjects remain to be elucidated.

  13. Measurements of radon concentrations in a sample representative of housing in Franche-Comte

    International Nuclear Information System (INIS)

    Aury, K.; Clinard, F.; Tillier, C.; Catelinois, O.; Pirard, P.; Aury, K.; Nourry, L.; Hochart, A.

    2008-01-01

    Three departments on four ones in Franche-Comte are classified at risk for radon: measurements are so compulsory in establishments receiving public. For the residential sector, no obligation of measurement are compulsory when french people spend 70% of their time in it. The data concerning homes are fragmentary and deserve to be completed. This campaign of measurements has confirmed the existence of radon in relatively high concentrations in Franche-Comte, including the sedimentary areas, justifying the necessity to realize a precise evaluation of the sanitary impact. The model will allow to study different strategies to reduce radon in houses. (N.C.)

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

    Science.gov (United States)

    Transgenic switchgrass (Panicum virgatum L.) has been produced for improved cell walls for biofuels. 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...

  15. Genetic Correlates of Maladaptive Beliefs: COMT VAL(158)MET and Irrational Cognitions Linked Depending on Distress.

    Science.gov (United States)

    Podina, Ioana; Popp, Radu; Pop, Ioan; David, Daniel

    2015-11-01

    Maladaptive/irrational beliefs are significant cognitive vulnerability mechanisms in psychopathology. They are more likely to be associated with a genetic vulnerability marker under conditions of emotional distress when irrational beliefs are more salient. Therefore, in the current study we investigated the COMT Val(158)Met gene variation in relation to irrational beliefs, assuming this relationship depended on the level of emotional distress. Two hundred and sixty-seven genotyped volunteers were assessed for core/general maladaptive beliefs, as well as trait emotional distress. We focused on context-independent measures of irrational beliefs and emotional distress in the absence of a stressor. As expected, the relationship between COMT Val(158)Met and irrational beliefs depended on the level of emotional distress (f(2)=.314). The COMT Val(158)Met-irrationality association was significant only when individuals fell in the average to above average range of emotional distress. Furthermore, within this range the Met allele seemed to relate to higher irrational beliefs. These results were significant for overall irrational beliefs and its subtypes, but not for rational beliefs, the functional counterpart of irrationality. In light of the study's limitations, the results should be considered as preliminary. If replicable, these findings have potential implications for therapygenetics, changing the view that COMT Val(158)Met might be of greater relevance when treatment modality does not rely on cognitive variables. Copyright © 2015. Published by Elsevier Ltd.

  16. COMT genetic variation confers risk for psychotic and affective disorders: a case control study

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    Lencz Todd

    2005-10-01

    Full Text Available Abstract Background Variation in the COMT gene has been implicated in a number of psychiatric disorders, including psychotic, affective and anxiety disorders. The majority of these studies have focused on the functional Val108/158Met polymorphism and yielded conflicting results, with limited studies examining the relationship between other polymorphisms, or haplotypes, and psychiatric illness. We hypothesized that COMT variation may confer a general risk for psychiatric disorders and have genotyped four COMT variants (Val158Met, rs737865, rs165599, and a SNP in the P2 promoter [-278A/G; rs2097603] in 394 Caucasian cases and 467 controls. Cases included patients with schizophrenia (n = 196, schizoaffective disorder (n = 62, bipolar disorder (n = 82, major depression (n = 30, and patients diagnosed with either psychotic disorder NOS or depressive disorder NOS (n = 24. Results SNP rs2097603, the Val/Met variant and SNP rs165599 were significantly associated (p = 0.004; p = 0.05; p = 0.035 with a broad "all affected" diagnosis. Haplotype analysis revealed a potentially protective G-A-A-A haplotype haplotype (-278A/G; rs737865; Val108/158Met; rs165599, which was significantly underrepresented in this group (p = 0.0033 and contained the opposite alleles of the risk haplotype previously described by Shifman et al. Analysis of diagnostic subgroups within the "all affecteds group" showed an association of COMT in patients with psychotic disorders as well as in cases with affective illness although the associated variants differed. The protective haplotype remained significantly underrepresented in most of these subgroups. Conclusion Our results support the view that COMT variation provides a weak general predisposition to neuropsychiatric disease including psychotic and affective disorders.

  17. Responses of catecholestrogen metabolism to acute graded exercise in normal menstruating women before and after training.

    Science.gov (United States)

    De Crée, C; Ball, P; Seidlitz, B; Van Kranenburg, G; Geurten, P; Keizer, H A

    1997-10-01

    It has been hypothesized that exercise-related hypo-estrogenemia occurs as a consequence of increased competition of catecholestrogens (CE) for catechol-O-methyltransferase (COMT). This may result in higher norepinephrine (NE) concentrations, which could interfere with normal gonadotropin pulsatility. The present study investigates the effects of training on CE responses to acute exercise stress. Nine untrained eumenorrheic women (mean percentage of body fat +/-SD: 24.8 +/- 3.1%) volunteered for an intensive 5-day training program. Resting, submaximal, and maximal (tmax) exercise plasma CE, estrogen, and catecholamine responses were determined pre- and post training in both the follicular (FPh) and luteal phase (LPh). Acute exercise stress increased total primary estrogens (E) but had little effect on total 2-hydroxyestrogens (2-OHE) and 2-hydroxyestrogen-monomethylethers (2-MeOE) (= O-methylated CE after competition for catechol-O-methyltransferase). This pattern was not significantly changed by training. However, posttraining LPh mean (+/-SE) plasma E, 2-OHE, and 2-MeOE concentrations were significantly lower (P Training produced opposite effects on 2-OHE:E ratios (an estimation of CE formation) during acute exercise in the FPh (reduction) and LPh (increase). The 2-MeOE:2-OHE ratio (an estimation of CE activity) showed significantly higher values at tmax in both menstrual phases after training (FPh: +11%; LPh: +23%; P training, NE values were significantly higher (P training lowers absolute concentrations of plasma estrogens and CE; the acute exercise challenge altered plasma estrogens but had little effect on CE; estimation of the formation and activity of CE suggests that formation and O-methylation of CE proportionately increases. These findings may be of importance for NE-mediated effects on gonadotropin release.

  18. Effects of tolcapone on working memory and brain activity in abstinent smokers: A proof-of-concept study

    Science.gov (United States)

    Ashare, Rebecca L.; Wileyto, E. Paul; Ruparel, Kosha; Goelz, Patricia M.; Hopson, Ryan D.; Valdez, Jeffrey N.; Gur, Ruben C.; Loughead, James; Lerman, Caryn

    2014-01-01

    Background Dopamine levels in the prefrontal cortex (PFC) are thought to play an important role in cognitive function and nicotine dependence. The catechol-O-methyltransferase (COMT) inhibitor tolcapone, an FDA-approved treatment for Parkinson’s disease, increases prefrontal dopamine levels, with cognitive benefits that may vary by COMT genotype. We tested whether tolcapone alters working memory-related brain activity and performance in abstinent smokers. Methods In this double-blind crossover study, 20 smokers completed 8 days of treatment with tolcapone and placebo. In both medication periods, smokers completed blood oxygen level-dependent (BOLD) fMRI scans while performing a working memory N-back task after 24 h of abstinence. Smokers were genotyped prospectively for the COMT val158met polymorphism for exploratory analysis. Results Compared to placebo, tolcapone modestly improved accuracy (p = 0.017) and enhanced suppression of activation in the ventromedial prefrontal cortex (vmPFC) (p = 0.002). There were no effects of medication in other a priori regions of interest (dorsolateral PFC, dorsal cingulate/medial prefrontal cortex, or posterior cingulate cortex). Exploratory analyses suggested that tolcapone led to a decrease in BOLD signal in several regions among smokers with val/val genotypes, but increased or remained unchanged among met allele carriers. Tolcapone did not attenuate craving, mood, or withdrawal symptoms compared to placebo. Conclusions Data from this proof-of-concept study do not provide strong support for further evaluation of COMT inhibitors as smoking cessation aids. PMID:24095246

  19. 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.

  20. Influence of COMT Val158Met polymorphism on emotional decision-making: A sex-dependent relationship?

    Science.gov (United States)

    Costa, Danielle de Souza; Bechara, Antoine; de Paula, Jonas Jardim; Romano-Silva, Marco Aurélio; Correa, Humberto; Lage, Guilherme Menezes; Miranda, Débora Marques de; Malloy-Diniz, Leandro Fernandes

    2016-12-30

    The biological underpinnings of sex-related differences in decision-making are still under-explored. The COMT gene is related to sexual dimorphism and with different choices made under uncertainty, albeit no study has specifically investigated a moderation effect of sex on the association between the COMT gene and the performance on decision-making paradigms. In this study, we investigated the influence of the COMT Val 158 Met polymorphism on Iowa Gambling Task (IGT) performance depending on sex in a healthy adult sample. Participants were 192 healthy adults (84 men and 108 women). The first 40 choices in the IGT were considered decisions under ambiguity and the last 60 choices decisions under risk. To test our moderation hypothesis we used a separate regressions approach. The results revealed a sex-dependent effect of COMT Va l 158 Met polymorphism on decision-making as measured by the IGT. Val/Val women showed the best performance in the last trials of the IGT. Therefore, the COMT Val 158 Met polymorphism may be considered a genetic marker underlying sex differences in decision-making. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. The modulatory influence of the functional COMT Val158Met polymorphism on lexical decisions and semantic priming.

    Science.gov (United States)

    Reuter, Martin; Montag, Christian; Peters, Kristina; Kocher, Anne; Kiefer, Markus

    2009-01-01

    The role of the prefrontal Cortex (PFC) in higher cognitive functions - including working memory, conflict resolution, set shifting and semantic processing - has been demonstrated unequivocally. Despite the great heterogeneity among tasks measuring these phenotypes, due in part to the different cognitive sub-processes implied and the specificity of the stimulus material used, there is agreement that all of these tasks recruit an executive control system located in the PFC. On a biochemical level it is known that the dopaminergic system plays an important role in executive control functions. Evidence comes from molecular genetics relating the functional COMT Val158Met polymorphism to working memory and set shifting. In order determine whether this pattern of findings generalises to linguistic and semantic processing, we investigated the effects of the COMT Val158Met polymorphism in lexical decision making using masked and unmasked versions of the semantic priming paradigm on N = 104 healthy subjects. Although we observed strong priming effects in all conditions (masked priming, unmasked priming with short/long stimulus asynchronies (SOAs), direct and indirect priming), COMT was not significantly related to priming, suggesting no reliable influence on semantic processing. However, COMT Val158Met was strongly associated with lexical decision latencies in all priming conditions if considered separately, explaining between 9 and 14.5% of the variance. Therefore, the findings indicate that COMT mainly influences more general executive control functions in the PFC supporting the speed of lexical decisions.

  2. The modulatory influence of the functional COMT Val158Met polymorphism on lexical decisions and semantic priming

    Directory of Open Access Journals (Sweden)

    Martin Reuter

    2009-08-01

    Full Text Available The role of the prefrontal Cortex (PFC in higher cognitive functions - including working memory, conflict resolution, set shifting and semantic processing - has been demonstrated unequivocally. Despite the great heterogeneity among tasks measuring these phenotypes, due in part to the different cognitive sub-processes implied and the specificity of the stimulus material used, there is agreement that all of these tasks recruit an executive control system located in the PFC. On a biochemical level it is known that the dopaminergic system plays an important role in executive control functions. Evidence comes from molecular genetics relating the functional COMT Val158Met polymorphism to working memory and set shifting. In order determine whether this pattern of findings generalises to linguistic and semantic processing, we investigated the effects of the COMT Val158Met polymorphism in lexical decision making using masked and unmasked versions of the semantic priming paradigm on N=104 healthy subjects. Although we observed strong priming effects in all conditions (masked priming, unmasked priming with short/long stimulus asynchronies (SOAs, direct and indirect priming, COMT was not significantly related to masked priming, suggesting no reliable influence on semantic processing. However, COMT Val158Met was strongly associated with lexical decision latencies in all priming conditions if considered separately, explaining between 9 to 14.5 % of the variance. Therefore, the findings indicate that COMT mainly influences more general executive control functions in the PFC supporting the speed of lexical decisions.

  3. 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…

  4. 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.

  5. Pharmacogenetic guidance: individualized medicine promotes enhanced pain outcomes

    Directory of Open Access Journals (Sweden)

    Dragic LL

    2017-12-01

    Full Text Available Lisa Lynn Dragic,1 Erica L Wegrzyn,2 Michael E Schatman,3–5 Jeffrey Fudin2,6 1Central Arkansas Veterans Healthcare System, Little Rock, AR, USA; 2Department of Pharmacy, Albany Stratton VA Medical Center, Albany, NY, USA; 3Research and Network Development, Boston Pain Care, Waltham, MA, USA; 4Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, USA; 5Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, USA; 6Scientific and Clinical Affairs, Remitigate, LLC, Delmar, NY, USA Abstract: The use of pharmacogenomics has become more prevalent over the past several years in treating many disease states. Several cytochrome P450 enzymes play a role in the metabolism of many pain medications including opioids and antidepressants. Noncytochrome P450 enzymes such as methylenetetrahydrofolate reductase (MTHFR and catechol-O-methyl transferase (COMT also play a role in the explanation of opioid dosage requirements as well as in response to certain antidepressants. We present the case of a patient with reduced COMT and MTHFR expression treated with leucovorin 10 mg daily for the management of chronic pain. The use of leucovorin in this patient decreased pain scores, which were clinically significant and increased functionality. This case demonstrates the importance of pharmacogenetics testing in patients, as this can help direct providers to better therapeutic options for their patients. Keywords: pharmacogenetic, depression, pain, MTHFR, COMT, methyl tetrahydrofolate reductase, catechol-O-methyltransferase

  6. The association between well-being and the COMT gene: Dispositional gratitude and forgiveness as mediators.

    Science.gov (United States)

    Liu, Jinting; Gong, Pingyuan; Gao, Xiaoxue; Zhou, Xiaolin

    2017-05-01

    Previous studies have demonstrated the contributions of genetic variants and positive psychological traits (e.g. gratitude and forgiveness) to well-being. However, little is known about how genes interact with positive traits to affect well-being. To investigate to what extent the COMT Val158Met polymorphism modulates well-being and to what extent dispositional gratitude and forgiveness mediate the individual differences in well-being, 445 participants were recruited and required to complete a battery of questionnaires. We found that individuals with a smaller number of the Met alleles reported greater well-being, less depressive symptoms, and greater tendencies for gratitude and forgiveness. Moreover, dispositional gratitude and forgiveness mediated the genotype effects on well-being and depressive symptoms. These results remained significant after controlling for non-genetic factors (socioeconomic status, religious beliefs, romantic relationship status, parenting style). The sample size limits the generalizability of results. This study demonstrates the contribution of the COMT Val158Met polymorphism to individual differences in well-being and suggests a potential psychobiological pathway from dopaminergic and noradrenergic systems to happiness. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Auguste Comte and Consensus Formation in American Religious Thought—Part 1: The Creation of Consensus

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    Kenneth S. Sacks

    2017-08-01

    Full Text Available French intellectual Auguste Comte was the most influential sociologist and philosopher of science in the Nineteenth Century. This first of two articles summarizes his complex life’s works and details reactions to them by Transcendentalists and Unitarians, from its American introduction in 1837 until just after the Civil War. Using public speeches and published essays, the article analyzes the ways in which intellectuals supported and criticized Comte’s theories. Because he wrote in such abstract and difficult French, criticisms centered not on the nuances of his work, but more superficially on his alleged atheism. These attacks occur because of a variety of consequences of the Civil War that had little to do directly with Comte’s philosophy. Instead, Comte was a convenient vehicle for expressing anxiety over a modernism that included an accelerated threat against religion posed by technology and science and the emerging dominance of that secular knowledge in universities. The second article will analyze Comte’s influence on later Transcendentalists and other post-Unitarian thinkers.

  8. 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

  9. 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 ...

  10. 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.

  11. 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)…

  12. 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......) 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...

  13. Common Variants in LRP2 and COMT Genes Affect the Susceptibility of Gout in a Chinese Population.

    Science.gov (United States)

    Dong, Zheng; Zhao, Dongbao; Yang, Chengde; Zhou, Jingru; Qian, Qiaoxia; Ma, Yanyun; He, Hongjun; Ji, Hengdong; Yang, Yajun; Wang, Xiaofeng; Xu, Xia; Pang, Yafei; Zou, Hejian; Jin, Li; Wang, Jiucun

    2015-01-01

    Gout is a common inflammation disease resulting from an increase in serum uric acid. Nearly 70% of uric acid is excreted via the kidneys. To date, evidence for an association between genetic loci and gout is absent, equivocal or not replicated. Our study aims to test variants in two genes abundantly expressed in the kidney, LRP2 and COMT, for their association with uric acid and gout. In total, 1318 Chinese individuals were genotyped for rs2544390 in LRP2 and rs4680 in COMT. These LRP2 and COMT gene polymorphisms showed no significant effect on uric acid (P = 0.204 and 0.188, separately); however, rs2544390 in LRP2 did influence uric acid levels in individuals with BMI ≥ 25 (P = 0.009). In addition, the allele frequency distributions of the two loci showed a significant difference between gout patients and healthy controls. A missense variation in rs4680 (G > A) decreased the risk of gout (OR = 0.77, P = 0.015), whereas the T allele of rs2544390 was associated with gout pathogenesis risk (OR = 1.26, P = 0.020). The present study provides the first evidence for an association between COMT and gout. Rs2544390 in LRP2 only influenced uric acid levels in individuals with BMI ≥ 25, which might explain the discrepant results among previous studies. In addition, we are the first to identify the association between LRP2 and gout in a Chinese population and to confirm this association in Asians.

  14. Dopamine and the Creative Mind: Individual Differences in Creativity Are Predicted by Interactions between Dopamine Genes DAT and COMT.

    Science.gov (United States)

    Zabelina, Darya L; Colzato, Lorenza; Beeman, Mark; Hommel, Bernhard

    2016-01-01

    The dopaminergic (DA) system may be involved in creativity, however results of past studies are mixed. We attempted to clarify this putative relation by considering the mediofrontal and the nigrostriatal DA pathways, uniquely and in combination, and their contribution to two different measures of creativity--an abbreviated version of the Torrance Test of Creative Thinking, assessing divergent thinking, and a real-world creative achievement index. We found that creativity can be predicted from interactions between genetic polymorphisms related to frontal (COMT) and striatal (DAT) DA pathways. Importantly, the Torrance test and the real-world creative achievement index related to different genetic patterns, suggesting that these two measures tap into different aspects of creativity, and depend on distinct, but interacting, DA sub-systems. Specifically, we report that successful performance on the Torrance test is linked with dopaminergic polymorphisms associated with good cognitive flexibility and medium top-down control, or with weak cognitive flexibility and strong top-down control. The latter is particularly true for the originality factor of divergent thinking. High real-world creative achievement, on the other hand, as assessed by the Creative Achievement Questionnaire, is linked with dopaminergic polymorphisms associated with weak cognitive flexibility and weak top-down control. Taken altogether, our findings support the idea that human creativity relies on dopamine, and on the interaction between frontal and striatal dopaminergic pathways in particular. This interaction may help clarify some apparent inconsistencies in the prior literature, especially if the genes and/or creativity measures were analyzed separately.

  15. Polimorfismo en el gen COMT en una muestra de gestantes normales y con restricción del crecimiento intrauterino en un hospital de Lima

    OpenAIRE

    José Pacheco-Romero; Doris Huerta; Oscar Acosta; Santiago Cabrera

    2013-01-01

    Antecedentes: Los procesos fisiopatológicos que ocurren a nivel celular y molecular en la restricción de crecimiento intrauterino (RCIU) son aún desconocidos. La catecol-O-metiltransferasa (COMT) es una enzima de fase II que inactiva los catecol estrógenos al transferir un grupo metílico. Se conoce un polimorfismo funcional Val158 Met en el gen COMT como un marcador susceptible para diversas enfermedades maternoperinatales, existiendo estudios que sugieren que el alelo que codifica una COMT d...

  16. Association between COMT Polymorphism Val158Met and Opioid Consumption in Patients with Postoperative Pain: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Bo Hu

    2018-01-01

    Full Text Available Background/Aims: Several factors influencing postoperative pain and the effect of opioid analgesics have been investigated on an individual level. The aim of this study was to clarify the impact of catecholamine-O-methyltransferase (COMT gene Val158Met on opioid consumption in postoperative patients. Methods: A systematic review and meta-analysis of the literature up to September 30, 2017, were performed by using PubMed, Cochrane Library, ISI Web of Science, and Chinese National Knowledge Infrastructure (CNKI database. The meta-analysis examined all studies involving the association between genetic polymorphisms of COMT Val158Met and opioid consumption during the acute postoperative period. Results: Of the 153 identified studies, 23 studies were retrieved for systematic review and 10 studies were retrieved for meta-analysis. However, it was impossible to conduct meta-analysis on the association between COMT Val158Met polymorphism and postoperative pain because of heterogeneity of the data. Overall, meta-analysis showed that COMT Val/Met carriers consumed less opioid for analgesia within the first 24 hours after surgery (SMD = 0.14, 95% CI = [0.03, 0.25], P = 0.01 but not within 48 hours (SMD = 0.14, 95% CI = [0.08, 0.36], P = 0.21. There was no significant difference in opioid consumption between Val/ Val and Met/Met patients. Conclusion: Patients with Val/Met but not Met/Met allele variant consumed less opioid, though larger and better-designed studies are required to obtain an exclusive conclusion about the correlation between postoperative pain and COMT Val158Met polymorphism.

  17. Lack of effect of polymorphisms in dopamine metabolism related genes on imaging of TRODAT-1 in striatum of asymptomatic volunteers and patients with Parkinson's disease.

    Science.gov (United States)

    Lynch, David R; Mozley, P David; Sokol, Set; Maas, Nicole M C; Balcer, Laura J; Siderowf, Andrew D

    2003-07-01

    SPECT scanning using (99)Tc-TRODAT-1, a ligand that binds to dopamine transporters, may be useful for detection of early Parkinson's disease (PD), diagnosis of presymptomatic individuals, and monitoring disease progression. Understanding whether genetic factors contribute to inter-individual variability is crucial for interpreting imaging results in the context of disease pathophysiology. We tested whether polymorphisms in the genes for catechol-O-methyltransferase (COMT), monoamine-oxidase B (MAO-B), and the dopamine transporter (DAT) influence dopamine uptake parameters in the striatum in vivo in asymptomatic volunteers and patients with PD as measured with (99)Tc-TRODAT-1. (99)Tc-TRODAT-1 binding declined with age in both asymptomatic volunteers and PD patients, and depended on disease duration in PD patients. We found no significant association between COMT, MAO-B, and DAT polymorphisms and results of (99)Tc-TRODAT-1 testing in asymptomatic volunteers or patients with PD. In PD patients, the age of disease onset and speed of progression did not differ based on these polymorphisms. These results demonstrate that these specific genetic variations do not alter the fidelity of (99)Tc-TRODAT-1 as a measure of dopaminergic function in asymptomatic volunteer individuals or patients with PD. Copyright 2003 Movement Disorder Society

  18. Dopamine and cognitive control: sex-by-genotype interactions influence the capacity to switch attention.

    Science.gov (United States)

    Gurvich, C; Rossell, S L

    2015-03-15

    Cognitive performance in healthy persons varies widely between individuals. Sex differences in cognition are well reported, and there is an emerging body of evidence suggesting that the relationship between dopaminergic neurotransmission, implicated in many cognitive functions, is modulated by sex. Here, we examine the influence of sex and genetic variations along the dopaminergic pathway on aspects of cognitive control. A total of 415 healthy individuals, selected from an international consortium linked to Brain Research and Integrative Neuroscience Network (BRAINnet), were genotyped for two common and functional genetic variations of dopamine regulating genes: the catechol-O-methyltransferase [COMT] gene (rs4680) and the dopamine receptor D2 [DRD2] gene (rs6277). Cognitive measures were selected to explore sustained attention (using a continuous performance task), switching of attention (using a Trails B adaptation) and working memory (a visual computerised adaptation of digit span). While there were no main effects for genotype across any tasks, analyses revealed significant sex by genotype interactions for the capacity to switch attention. In relation to COMT, superior performance was noted in females with the Val/Val genotype and for DRD2, superior performance was seen for TT females and CC males. These findings highlight the importance of considering genetic variation in baseline dopamine levels in addition to sex, when considering the impact of dopamine on cognition in healthy populations. These findings also have important implications for the many neuropsychiatric disorders that implicate dopamine, cognitive changes and sex differences. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Genetic predictor of working memory and prefrontal function in women with HIV.

    Science.gov (United States)

    Sundermann, Erin E; Bishop, Jeffrey R; Rubin, Leah H; Little, Deborah M; Meyer, Vanessa J; Martin, Eileen; Weber, Kathleen; Cohen, Mardge; Maki, Pauline M

    2015-02-01

    The Val158Met (rs4680) single-nucleotide polymorphism (SNP) of the catechol-O-methyltransferase gene (COMT) influences executive function and prefrontal function through its effect on dopamine (DA) metabolism. Both HIV and the Val allele of the Val158Met SNP are associated with compromised executive function and inefficient prefrontal function. The present study used behavioral and neuroimaging techniques to determine independent and interactive associations between HIV serostatus and COMT genotype on working memory and prefrontal function in women. For the behavioral study, 54 HIV-infected and 33 HIV-uninfected women completed the 0-, 1-, and 2-back conditions of the verbal N-back, a working memory test. For the imaging study, 36 women (23 HIV-infected, 13 HIV-uninfected) underwent functional magnetic resonance imaging (fMRI) assessments while completing the N-back task. HIV-infected women demonstrated significantly worse N-back performance compared with HIV-uninfected women (p women performed significantly worse than HIV-uninfected controls across N-back conditions (p working memory deficits and altered prefrontal function in HIV-infected individuals.

  20. Identifying new susceptibility genes on dopaminergic and serotonergic pathways for the framing effect in decision-making.

    Science.gov (United States)

    Gao, Xiaoxue; Liu, Jinting; Gong, Pingyuan; Wang, Junhui; Fang, Wan; Yan, Hongming; Zhu, Lusha; Zhou, Xiaolin

    2017-09-01

    The framing effect refers the tendency to be risk-averse when options are presented positively but be risk-seeking when the same options are presented negatively during decision-making. This effect has been found to be modulated by the serotonin transporter gene (SLC6A4) and the catechol-o-methyltransferase gene (COMT) polymorphisms, which are on the dopaminergic and serotonergic pathways and which are associated with affective processing. The current study aimed to identify new genetic variations of genes on dopaminergic and serotonergic pathways that may contribute to individual differences in the susceptibility to framing. Using genome-wide association data and the gene-based principal components regression method, we examined genetic variations of 26 genes on the pathways in 1317 Chinese Han participants. Consistent with previous studies, we found that the genetic variations of the SLC6A4 gene and the COMT gene were associated with the framing effect. More importantly, we demonstrated that the genetic variations of the aromatic-L-amino-acid decarboxylase (DDC) gene, which is involved in the synthesis of both dopamine and serotonin, contributed to individual differences in the susceptibility to framing. Our findings shed light on the understanding of the genetic basis of affective decision-making. © The Author (2017). Published by Oxford University Press.

  1. Interactions Between Variation in Candidate Genes and Environmental Factors in the Etiology of Schizophrenia and Bipolar Disorder: a Systematic Review.

    Science.gov (United States)

    Misiak, Błażej; Stramecki, Filip; Gawęda, Łukasz; Prochwicz, Katarzyna; Sąsiadek, Maria M; Moustafa, Ahmed A; Frydecka, Dorota

    2017-08-18

    Schizophrenia and bipolar disorder (BD) are complex and multidimensional disorders with high heritability rates. The contribution of genetic factors to the etiology of these disorders is increasingly being recognized as the action of multiple risk variants with small effect sizes, which might explain only a minor part of susceptibility. On the other site, numerous environmental factors have been found to play an important role in their causality. Therefore, in recent years, several studies focused on gene × environment interactions that are believed to bridge the gap between genetic underpinnings and environmental insults. In this article, we performed a systematic review of studies investigating gene × environment interactions in BD and schizophrenia spectrum phenotypes. In the majority of studies from this field, interacting effects of variation in genes encoding catechol-O-methyltransferase (COMT), brain-derived neurotrophic factor (BDNF), and FK506-binding protein 5 (FKBP5) have been explored. Almost consistently, these studies revealed that polymorphisms in COMT, BDNF, and FKBP5 genes might interact with early life stress and cannabis abuse or dependence, influencing various outcomes of schizophrenia spectrum disorders and BD. Other interactions still require further replication in larger clinical and non-clinical samples. In addition, future studies should address the direction of causality and potential mechanisms of the relationship between gene × environment interactions and various categories of outcomes in schizophrenia and BD.

  2. Identifying new susceptibility genes on dopaminergic and serotonergic pathways for the framing effect in decision-making

    Science.gov (United States)

    Gao, Xiaoxue; Liu, Jinting; Gong, Pingyuan; Wang, Junhui; Fang, Wan; Yan, Hongming; Zhu, Lusha

    2017-01-01

    Abstract The framing effect refers the tendency to be risk-averse when options are presented positively but be risk-seeking when the same options are presented negatively during decision-making. This effect has been found to be modulated by the serotonin transporter gene (SLC6A4) and the catechol-o-methyltransferase gene (COMT) polymorphisms, which are on the dopaminergic and serotonergic pathways and which are associated with affective processing. The current study aimed to identify new genetic variations of genes on dopaminergic and serotonergic pathways that may contribute to individual differences in the susceptibility to framing. Using genome-wide association data and the gene-based principal components regression method, we examined genetic variations of 26 genes on the pathways in 1317 Chinese Han participants. Consistent with previous studies, we found that the genetic variations of the SLC6A4 gene and the COMT gene were associated with the framing effect. More importantly, we demonstrated that the genetic variations of the aromatic-L-amino-acid decarboxylase (DDC) gene, which is involved in the synthesis of both dopamine and serotonin, contributed to individual differences in the susceptibility to framing. Our findings shed light on the understanding of the genetic basis of affective decision-making. PMID:28431168

  3. Norepinephrine metabolism in neuronal cultures is increased by angiotensin II

    International Nuclear Information System (INIS)

    Sumners, C.; Shalit, S.L.; Kalberg, C.J.; Raizada, M.K.

    1987-01-01

    In this study the authors have examined the actions of angiotensin II (ANG II) on catecholamine metabolism in neuronal brain cell cultures prepared from the hypothalamus and brain stem. Neuronal cultures prepared from the brains of 1-day-old Sprague-Dawley rats exhibit specific neuronal uptake mechanisms for both norepinephrine (NE) and dopamine (DA), and also monoamine oxidase (MAO) and catechol O-methyltransferase (COMT) activity. Separate neuronal uptake sites for NE and DA were identified by using specific neuronal uptake inhibitors for each amine. In previous studies, they determined that ANG II (10 nM-1 μM) stimulates increased neuronal [ 3 H]NE uptake by acting as specific receptors. They have confirmed these results here and in addition have shown that ANG II has not significant effects on neuronal [ 3 H]DA uptake. These results suggest that the actions of ANG II are restricted to the NE transporter in neuronal cultures. It is possible that ANG II stimulates the intraneuronal metabolism of at least part of the NE that is taken up, because the peptide stimulates MAO activity, an effect mediated by specific ANG II receptors. ANG II had no effect on COMT activity in neuronal cultures. Therefore, the use of neuronal cultures of hypothalamus and brain stem they have determined that ANG II can specifically alter NE metabolism in these areas, while apparently not altering DA metabolism

  4. Both COMT Val158Met single nucleotide polymorphism and sex-dependent differences influence response inhibition

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    Valentina eMione

    2015-05-01

    Full Text Available Reactive and proactive control of actions are cognitive abilities that allow to deal with a continuously changing environment by adjusting already programmed actions. They also set forthcoming acts by evaluating the outcome of the previous ones. Earlier studies highlighted sex related differences in the strategies and in the pattern of brain activation during cognitive tasks involving reactive and proactive control. To further identify sex-dependent characteristics in the cognitive control of actions, in this study we have assessed whether/how differences in reactive and proactive control were modulated by the COMT Val158Met single nucleotide polymorphism, a genetic factor known to influence the functionality of the dopaminergic system, in particular at the level of prefrontal cortex. Two groups of male and female participants were further sorted according to their genotype (Val/Met, Val/Val and Met/Met and tested in a stop signal task, a consolidated tool to measure reactive and proactive control in experimental and clinical settings. In each group of participants we estimated both a measure of the capacity to react to unexpected events and the ability of monitoring their performance. The between groups comparison of these measures indicated a poorer ability of male individuals carrying the Val/Val genotype in error-monitoring, suggesting that differences between sexes could be influenced by the efficiency of COMT and that other sex-specific factors have to be considered. The comprehension of inter-groups behavioral and physiological correlates of cognitive control will provide more accurate diagnostic tools for predicting the incidence and the development of pathologies like ADHD or deviant behaviors as drug or alcohol abuse.

  5. O Ateísmo Francês Contemporâneo: uma comparação crítica entre Michel Onfray e André Compte-Sponville (Contemporary French Atheism: a Critical Comparison between Michel Onfray and André Comte-Sponville - DOI: 10.5752/P.2175-5841.2010v8n18p127

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    Agnaldo Cuoco Portugal

    2011-04-01

    Full Text Available Michel Onfray e André Comte-Sponville são os dois mais famosos representantes do ateísmo filosófico francês contemporâneo, que continua uma tradição iniciada no século XVIII de negação irreligiosa da noção monoteísta de Deus. Embora compartilhando várias ideias, como o naturalismo e, obviamente, a rejeição do monoteísmo, suas propostas têm diferenças importantes. Onfray imputa à religião a maioria dos males enfrentados pela humanidade, recusando-se a fazer qualquer concessão à tradição religiosa monoteísta, e propondo uma filosofia libertária de tipo hedonista e materialista. Comte-Sponville vê aspectos positivos na religião no tocante à manutenção da unidade social e propõe uma espiritualidade mística ateia. O artigo faz uma breve apresentação de suas teses e formula críticas a ambas as propostas. Onfray está muito mais preocupado em convencer de uma proposta política do que em argumentar filosoficamente em favor de uma tese e Comte-Sponville não parece perceber as consequências auto-refutadoras do naturalismo, que também torna muito problemática a própria noção de moralidade. Palavras-chave: Michel Onfray; Comte-Sponville; ateísmo; neoateísmo; naturalismo.  Abstract Michel Onfray and André Comte-Sponville are the most famous representatives of philosophical contemporary French atheism, which is a continuation of a tradition begun in the 18th Century of irreligious denying of the monotheistic notion of God. Although sharing many ideas, like naturalism and, obviously, the rejection of the monotheistic conception of God, their proposals show important distinctions. Onfray blames on religion most of evils faced by humanity, refusing to make any concession to monotheism, and proposing a libertarian, hedonistic, materialistic philosophy. Comte-Sponville sees positive aspects in religion regarding the keeping of social unity, and puts forward an atheistic spirituality. The article makes a brief

  6. Common Variants in LRP2 and COMT Genes Affect the Susceptibility of Gout in a Chinese Population.

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    Zheng Dong

    Full Text Available Gout is a common inflammation disease resulting from an increase in serum uric acid. Nearly 70% of uric acid is excreted via the kidneys. To date, evidence for an association between genetic loci and gout is absent, equivocal or not replicated. Our study aims to test variants in two genes abundantly expressed in the kidney, LRP2 and COMT, for their association with uric acid and gout. In total, 1318 Chinese individuals were genotyped for rs2544390 in LRP2 and rs4680 in COMT. These LRP2 and COMT gene polymorphisms showed no significant effect on uric acid (P = 0.204 and 0.188, separately; however, rs2544390 in LRP2 did influence uric acid levels in individuals with BMI ≥ 25 (P = 0.009. In addition, the allele frequency distributions of the two loci showed a significant difference between gout patients and healthy controls. A missense variation in rs4680 (G > A decreased the risk of gout (OR = 0.77, P = 0.015, whereas the T allele of rs2544390 was associated with gout pathogenesis risk (OR = 1.26, P = 0.020. The present study provides the first evidence for an association between COMT and gout. Rs2544390 in LRP2 only influenced uric acid levels in individuals with BMI ≥ 25, which might explain the discrepant results among previous studies. In addition, we are the first to identify the association between LRP2 and gout in a Chinese population and to confirm this association in Asians.

  7. COMT Val158Met genotype is associated with reward learning: A replication study and meta-analysis

    Science.gov (United States)

    Corral-Frías, Nadia S.; Pizzagalli, Diego A.; Carré, Justin; Michalski, Lindsay J; Nikolova, Yuliya S.; Perlis, Roy H.; Fagerness, Jesen; Lee, Mary R.; Conley, Emily Drabant; Lancaster, Thomas M.; Haddad, Stephen; Wolf, Aaron; Smoller, Jordan W.; Hariri, Ahmad R.; Bogdan, Ryan

    2016-01-01

    Identifying mechanisms through which individual differences in reward learning emerge offers an opportunity to understand both a fundamental form of adaptive responding as well as etiological pathways through which aberrant reward learning may contribute to maladaptive behaviors and psychopathology. One candidate mechanism through which individual differences in reward learning may emerge is variability in dopaminergic reinforcement signaling. A common functional polymorphism within the catechol-O-methyl transferase gene (COMT; rs4680, Val158Met) has been linked to reward learning where homozygosity for the Met allele (associated with heightened prefrontal dopamine function and decreased dopamine synthesis in the midbrain) has been associated with relatively increased reward learning. Here, we used a probabilistic reward learning task to asses response bias, a behavioral form of reward learning, across 3 separate samples that were combined for analyses (age: 21.80 ± 3.95; n=392; 268 female; European-American, n=208). We replicate prior reports that COMT rs4680 Met allele homozygosity is associated with increased reward learning in European-American participants (β=0.20, t= 2.75, p< 0.01; ΔR2= 0.04). Moreover, a meta-analysis of 4 studies, including the current one, confirmed the association between COMT rs4680 genotype and reward learning (95% CI −0.11 to −0.03; z=3.2; p<0.01). These results suggest that variability in dopamine signaling associated with COMT rs4680 influences individual differences in reward which may potentially contribute to psychopathology characterized by reward dysfunction. PMID:27138112

  8. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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    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.

  10. [Effects of anxiety and the COMT gene on cortical evoked potentials and performance effectiveness of selective attention].

    Science.gov (United States)

    Alfimova, M V; Golimbet, V E; Lebedeva, I S; Korovaĭtseva, G I; Lezheĭko, T V

    2014-01-01

    We studied influence of the anxiety-related trait Harm Avoidance and the COMT gene, which is an important modulator of prefrontal functioning, on event-related potentials in oddball paradigm and performance effectiveness of selective attention. For 50 individuals accuracy and time of searching words among letters at any desired rate and then under an instruction to perform the task as quickly and accurate as possible were measured. Scores on the Harm Avoidance scale from Cloninger's Temperament and Character Inventory, N100 and P300 parameters, and COMTVa1158Met genotypes were obtained for them as well. Searching accuracy and time were mainly related to N100 amplitude. The COMT genotype and Harm Avoidance did not affect N100 amplitude; however, the N100 amplitude modulated their effects on accuracy and time dynamics. Harm Avoidance was positively correlated with P300 latency. The results suggest that anxiety and the COMT gene effects on performance effectiveness of selective attention depend on cognitive processes reflected in N100 parameters.

  11. Why some people discount more than others: Baseline activation in the dorsal PFC mediates the link between COMT genotype and impatient choice

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    Lorena R. R. Gianotti

    2012-05-01

    Full Text Available Individuals differ widely in how steeply they discount future rewards. The sources of these stable individual differences in delay discounting (DD are largely unknown. One candidate is the COMT Val158Met polymorphism, known to modulate prefrontal dopamine levels and affect DD. To identify possible neural mechanisms by which this polymorphism may contribute to stable individual DD differences, we measured 73 participants’ neural baseline activation using resting electroencephalogram (EEG. Such neural baseline activation measures are highly heritable and stable over time, thus an ideal endophenotype candidate to explain how genes may influence behavior via individual differences in neural function. After EEG-recording, participants made a series of incentive-compatible intertemporal choices to determine the steepness of their DD. We found that COMT significantly affected DD and that this effect was mediated by baseline activation level in the left dorsal prefrontal cortex (DPFC: (i COMT had a significant effect on DD such that the number of Val alleles was positively correlated with steeper DD (higher numbers of Val alleles means greater COMT activity and thus lower dopamine levels. (ii A whole-brain search identified a cluster in left DPFC where baseline activation was correlated with DD; lower activation was associated with steeper DD. (iii COMT had a significant effect on the baseline activation level in this left DPFC cluster such that a higher number of Val alleles was associated with lower baseline activation. (iv The effect of COMT on DD was explained by the mediating effect of neural baseline activation in the left DPFC cluster. Our study thus establishes baseline activation level in left DPFC as salient neural signature in the form of an endophenotype that mediates the link between COMT and DD.

  12. Polimorfismo en el gen COMT en una muestra de gestantes normales y con restricción del crecimiento intrauterino en un hospital de Lima

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    José Pacheco-Romero

    2013-04-01

    Full Text Available Antecedentes: Los procesos fisiopatológicos que ocurren a nivel celular y molecular en la restricción de crecimiento intrauterino (RCIU son aún desconocidos. La catecol-O-metiltransferasa (COMT es una enzima de fase II que inactiva los catecol estrógenos al transferir un grupo metílico. Se conoce un polimorfismo funcional Val158 Met en el gen COMT como un marcador susceptible para diversas enfermedades maternoperinatales, existiendo estudios que sugieren que el alelo que codifica una COMT de baja actividad puede ser un marcador susceptible para RCIU. Por lo tanto, el estudio del polimorfismo COMT ofrece una nueva estrategia para la evaluación de marcadores genéticos que pueden ser utilizados para la detección de ciertas alteraciones asociadas al embarazo. Objetivos: Establecer la asociación entre el polimorfismo Val158Met catecol-O-metiltransferasa (COMT y la restricción de crecimiento intrauterino. Institución: Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú. Diseño: Estudio tipo relacional (asociativo, con diseño observacional, tipo caso-control (no experimental. Materiales: Muestra de sangre materna de parturientas. Métodos: Durante el año 2011, se obtuvo 81 muestras para genotipaje del gen COMT. De ellas, 26 (32,1% correspondieron a parturientas con RCIU (casos y 55 (67,9% a muestras de madres de hijos sin RCIU (controles. La distribución de los genotipos fue evaluada usando la prueba de chi cuadrado. Se comprobó la distribución proporcional de los genotipos en los grupos con RCIU y sin RCIU con la hipótesis nula de Hardy-Weinberg. Las madres participantes firmaron un consentimiento informado. Principales medidas de resultados: Asociación entre los genotipos COMT y la RCIU, y entre los alelos COMT Val/Met y la RCIU. Resultados: Las distribuciones de los genotipos en los grupos con RCIU y sin RCIU estuvieron de acuerdo a la hipótesis nula de Hardy-Weinberg. Al relacionar los genotipos COMT Val

  13. Leptospirosis in Franche-Comté (FRANCE): clinical, biological, and therapeutic data.

    Science.gov (United States)

    Estavoyer, J M; Chirouze, C; Faucher, J F; Floret, N; Couetdic, G; Leroy, J; Hoen, B

    2013-09-01

    We report the patient data in 77 cases of leptospirosis confirmed by PCR and/or serology (micro-agglutination), observed between 1994 and 2008 at the Besançon teaching hospital. Our aim was to compare the epidemiological, clinical, biological, and therapeutic characteristics of leptospirosis in the Franche-Comté region, to those reported in other regions. The median age was 42years and 95% were male patients. Leptospirosis acquisition was likely related to aquatic leisure activities (50.6%), professional exposure (28.6%), building maintenance works (11.7%), or unknown (9.1%). Forty-eight cases were uncomplicated and 29 were severe presentations of leptospirosis. Among severe cases, eight patients had to be managed in an intensive care unit, and one patient died. L. grippotyphosa and L. icterohaemorrhagiae were the main serogroups involved. Age above 50years and serogroup L. icterohaemorrhagiae were positively associated with clinical severity. The outcome was favorable for 15 patients treated with ceftriaxone for less than 7days. We recommended conducting clinical trials aiming at validating short courses of ceftriaxone to treat leptospirosis. Copyright © 2013. Published by Elsevier SAS.

  14. Analysis of CYP1A1 and COMT polymorphisms in women with cervical cancer.

    Science.gov (United States)

    Kleine, J P; Camargo-Kosugi, C M; Carvalho, C V; Silva, F C; Silva, I D C G

    2015-12-29

    The aim of this case-control study was to obtain a comprehensive panel of genetic polymorphisms present only in genes (cytochrome P-450 1A1--CYP1A1 and catechol-O-methyl transferase--COMT) within the metabolic pathway of sex steroids and determine their possible associations with the presence or absence of cervical cancer. Genotypes of 222 women were analyzed: a) 81 with cancer of the cervix treated at the Cancer Hospital Alfredo Abram, between June 2012 and May 2013, with diagnosis confirmed surgically and/or through histomorphological examination; and b) 141 healthy women who assisted at the Endocrine Gynecology and Climacteric Ambulatory, Department of Gynecology, UNIFESP-EPM. These polymorphisms were detected by polymerase chain reaction amplification-restriction fragment length polymorphism analysis and visualized on 3% agarose gels stained with ethidium bromide. We found a significant association between the frequency of the CYP1A1 polymorphism and the development of cervical cancer. A statistical difference was observed between patient and control groups for CYP1A1 polymorphism genotype distributions (P 0.05) or between other risk variables analyzed. The CYP1A1 gene involved in the metabolic pathway of sex steroids might influence the emergence of pathological conditions such as cervical cancer in women who carry a mutated allele, and result in 1.80 and 13.46 times increased risk for women with heterozygous or homozygous mutated genotypes, respectively.

  15. The role of COMT and plasma proline in the variable penetrance of autistic spectrum symptoms in 22q11.2 deletion syndrome.

    Science.gov (United States)

    Hidding, E; Swaab, H; de Sonneville, L M J; van Engeland, H; Vorstman, J A S

    2016-11-01

    This paper examines how COMT 158 genotypes and plasma proline levels are associated with variable penetrance of social behavioural and social cognitive problems in 22q11.2 deletion syndrome (22q11DS). Severity of autistic spectrum symptoms of 45 participants with 22q11DS was assessed using the Autism Diagnostic Interview Revised. Face and facial emotion recognition was evaluated using standardized computer-based test-paradigms. Associations with COMT 158 genotypes and proline levels were examined. High proline levels and poor face recognition in individuals with the COMT MET allele, and poor facial emotion recognition, explained almost 50% of the variance in severity of autism symptomatology in individuals with 22q11DS. High proline levels and a decreased capacity to break down dopamine as a result of the COMT MET variant are both relevant in the expression of the social phenotype in patients. This epistatic interaction effect between the COMT 158 genotype and proline on the expression of social deficits in 22q11DS shows how factors other than the direct effects of the deletion itself can modulate the penetrance of associated cognitive and behavioural outcomes. These findings are not only relevant to our insight into 22q11DS, but also provide a model to better understand the phenomenon of variable penetrance in other pathogenic genetic variants. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. 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

    2009-11-01

    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 ratings of social phobia (etap (2) = 0.06). Analyses also indicated associations of BDNF genotype with parent-rated ADHD (p = 0.01, etap (2) = 0.10) and teacher-rated tics (p = 0.04; etap (2) = 0.07). There was also evidence of a possible interaction (p = 0.02, etap (2) = 0.09) of BDNF genotype with DAT1 3' VNTR with tic severity. BDNF and COMT may be biomarkers for phenotypic variation in ASD, but these preliminary findings remain tentative pending replication with larger, independent samples.

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  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 V; 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. Polimorfismo del gen de la catecol-O-metiltransferasa (COMT) en gestantes con restricción del crecimiento intrauterino (RCIU)

    OpenAIRE

    Pacheco, José; Huerta, Doris; Acosta, Oscar; Cabrera, Santiago

    2013-01-01

    Objetivos: Establecer la asociación entre el polimorfismo Vall58Met catecol-O-metiltransferasa (COMT) y la RCIU. Diseño: Estudio relacional, observacional, tipo caso-control. Institución: Facultad de Medicina, UNMSM. Participantes: Gestantes sin y con RCIU. Intervenciones: Se obtuvo 81 muestras de sangre para genotipaje del gen COMT; 55 (67,9%) correspondieron a gestantes sin RCIU (controles) y 26 (32,1%) a madres de hijos con RCIU. Las gestantes firmaron consentimiento informado. Principales...

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

    OpenAIRE

    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 ratings of social phobia (ηp2 = 0.06). Analyses also indicated associations of BDNF genotype with parent-rated ADHD (p = 0.01, ηp2 = 0.10) and teacher-rated ...

  2. Xenobiotic Metabolizing Gene Variants and Renal Cell Cancer: A Multicenter Study

    Energy Technology Data Exchange (ETDEWEB)

    Heck, Julia E. [International Agency for Research on Cancer, Lyon (France); Department of Epidemiology, School of Public Health, University of California Los Angeles, Los Angeles, CA (United States); Moore, Lee E. [Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (United States); Lee, Yuan-Chin A. [International Agency for Research on Cancer, Lyon (France); Department of Epidemiology, School of Public Health, University of California Los Angeles, Los Angeles, CA (United States); McKay, James D. [International Agency for Research on Cancer, Lyon (France); Hung, Rayjean J. [Samuel Lunenfeld Research Institute of Mount Sinai Hospital, Toronto, ON (Canada); Karami, Sara [Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (United States); Gaborieau, Valérie [International Agency for Research on Cancer, Lyon (France); Szeszenia-Dabrowska, Neonila [Department of Epidemiology, Institute of Occupational Medicine, Lodz (Poland); Zaridze, David G. [Cancer Research Centre, Institute of Carcinogenesis, Moscow (Russian Federation); Mukeriya, Anush [Cancer Research Centre, Department of Epidemiology, Moscow (Russian Federation); Mates, Dana [Institute of Public Health, Bucharest (Romania); Foretova, Lenka [Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno (Czech Republic); Janout, Vladimir; Kollárová, Helena [Department of Preventive Medicine, Faculty of Medicine, Palacky University, Olomouc (Czech Republic); Bencko, Vladimir [First Faculty of Medicine, Institute of Hygiene and Epidemiology, Charles University in Prague, Prague, Czech Republic (Czech Republic); Rothman, Nathaniel [Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (United States); Brennan, Paul [International Agency for Research on Cancer, Lyon (France); Chow, Wong-Ho [Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (United States); Boffetta, Paolo, E-mail: paolo.boffetta@mssm.edu [International Prevention Research Institute, Lyon (France); Tisch Cancer Institute, Mt. Sinai School of Medicine, New York, NY (United States)

    2012-02-20

    Background: The countries of Central and Eastern Europe have among the highest worldwide rates of renal cell cancer (RCC). Few studies have examined whether genetic variation in xenobiotic metabolic pathway genes may modify risk for this cancer. Methods: The Central and Eastern Europe Renal Cell Cancer study was a hospital-based case–control study conducted between 1998 and 2003 across seven centers in Central and Eastern Europe. Detailed data were collected from 874 cases and 2053 controls on demographics, work history, and occupational exposure to chemical agents. Genes [cytochrome P-450 family, N-acetyltransferases, NAD(P)H:quinone oxidoreductase I (NQO1), microsomal epoxide hydrolase (mEH), catechol-O-methyltransferase (COMT), uridine diphosphate-glucuronosyltransferase (UGT)] were selected for the present analysis based on their putative role in xenobiotic metabolism. Haplotypes were calculated using fastPhase. Odds ratios and 95% confidence intervals were estimated by unconditional logistic regression adjusted for country of residence, age, sex, smoking, alcohol intake, obesity, and hypertension. Results: We observed an increased risk of RCC with one SNP. After adjustment for multiple comparisons it did not remain significant. Neither NAT1 nor NAT2 slow acetylation was associated with disease. Conclusion: We observed no association between this pathway and renal cell cancer.

  3. Xenobiotic Metabolizing Gene Variants and Renal Cell Cancer: A Multicenter Study

    International Nuclear Information System (INIS)

    Heck, Julia E.; Moore, Lee E.; Lee, Yuan-Chin A.; McKay, James D.; Hung, Rayjean J.; Karami, Sara; Gaborieau, Valérie; Szeszenia-Dabrowska, Neonila; Zaridze, David G.; Mukeriya, Anush; Mates, Dana; Foretova, Lenka; Janout, Vladimir; Kollárová, Helena; Bencko, Vladimir; Rothman, Nathaniel; Brennan, Paul; Chow, Wong-Ho; Boffetta, Paolo

    2012-01-01

    Background: The countries of Central and Eastern Europe have among the highest worldwide rates of renal cell cancer (RCC). Few studies have examined whether genetic variation in xenobiotic metabolic pathway genes may modify risk for this cancer. Methods: The Central and Eastern Europe Renal Cell Cancer study was a hospital-based case–control study conducted between 1998 and 2003 across seven centers in Central and Eastern Europe. Detailed data were collected from 874 cases and 2053 controls on demographics, work history, and occupational exposure to chemical agents. Genes [cytochrome P-450 family, N-acetyltransferases, NAD(P)H:quinone oxidoreductase I (NQO1), microsomal epoxide hydrolase (mEH), catechol-O-methyltransferase (COMT), uridine diphosphate-glucuronosyltransferase (UGT)] were selected for the present analysis based on their putative role in xenobiotic metabolism. Haplotypes were calculated using fastPhase. Odds ratios and 95% confidence intervals were estimated by unconditional logistic regression adjusted for country of residence, age, sex, smoking, alcohol intake, obesity, and hypertension. Results: We observed an increased risk of RCC with one SNP. After adjustment for multiple comparisons it did not remain significant. Neither NAT1 nor NAT2 slow acetylation was associated with disease. Conclusion: We observed no association between this pathway and renal cell cancer.

  4. Sleep duration, depression, and oxytocinergic genotype influence prepulse inhibition of the startle reflex in postpartum women.

    Science.gov (United States)

    Comasco, Erika; Gulinello, Maria; Hellgren, Charlotte; Skalkidou, Alkistis; Sylven, Sara; Sundström-Poromaa, Inger

    2016-04-01

    The postpartum period is characterized by a post-withdrawal hormonal status, sleep deprivation, and susceptibility to affective disorders. Postpartum mothering involves automatic and attentional processes to screen out new external as well as internal stimuli. The present study investigated sensorimotor gating in relation to sleep duration, depression, as well as catecholaminergic and oxytocinergic genotypes in postpartum women. Prepulse inhibition (PPI) of the startle reflex and startle reactivity were assessed two months postpartum in 141 healthy and 29 depressed women. The catechol-O-methyltransferase (COMT) Val158Met, and oxytocin receptor (OXTR) rs237885 and rs53576 polymorphisms were genotyped, and data on sleep duration were collected. Short sleep duration (less than four hours in the preceding night) and postpartum depression were independently associated with lower PPI. Also, women with postpartum depression had higher startle reactivity in comparison with controls. The OXTR rs237885 genotype was related to PPI in an allele dose-dependent mode, with T/T healthy postpartum women carriers displaying the lowest PPI. Reduced sensorimotor gating was associated with sleep deprivation and depressive symptoms during the postpartum period. Individual neurophysiological vulnerability might be mediated by oxytocinergic genotype which relates to bonding and stress response. These findings implicate the putative relevance of lower PPI of the startle response as an objective physiological correlate of liability to postpartum depression. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  5. Fitting the pieces together: current research on the genetic basis of attention-deficit/hyperactivity disorder (ADHD

    Directory of Open Access Journals (Sweden)

    Evangelia Stergiakouli

    2010-08-01

    Full Text Available Evangelia Stergiakouli, Anita ThaparDepartment of Psychological Medicine and Neurology, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, United KingdomAbstract: Attention-deficit/hyperactivity disorder (ADHD is a highly disruptive childhood-onset disorder that often persists into adolescence and adulthood. Comorbidity with other problems, such as autism, dyslexia and conduct disorder (CD is very common. Although little is known about the pathophysiology of ADHD, family, twin and adoption studies have shown that it is highly heritable. Whole genome linkage studies suggest there are no common susceptibility genes of moderate effect size. Most published research has been based on functional candidate gene studies. The most consistent evidence for association with ADHD relates to a dopamine D4 receptor (DRD4 gene variable number tandem repeat (VNTR, a dopamine D5 receptor (DRD5 gene microsatellite and a dopamine transporter (DAT1 gene VNTR. In addition, the catechol-O-methyltransferase (COMT val158/108 met variant has been shown to increase risk for associated antisocial behavior. The first genome-wide association studies (GWAS of ADHD have been completed and although larger studies are still required to detect common risk variants, novel risk pathways are being suggested for ADHD. Further research on the contribution of rare variants, larger genome-wide association and sequencing studies and ADHD phenotype refinement is now needed.Keywords: attention-deficit/hyperactivity disorder (ADHD, genetics, molecular genetics, genome-wide association study (GWAS, gene-environment interplay

  6. Gene expression of drug metabolizing enzymes in adult and aged mouse liver: A modulation by immobilization stress

    International Nuclear Information System (INIS)

    Mikhailova, O.N.; Gulyaeva, L.F.; Filipenko, M.L.

    2005-01-01

    The role of stress in the regulation of enzymatic systems involved in the biotransformation of xenobiotics, as well as endogenous substrates in the liver was investigated using single immobilization stress as a model. Adult (3 months of age) and aged (26 months) C3H/a male mice were used. Cytochrome P450 1A1 and 1A2 (CYP1A1 and CYP1A2), glutathione S-transferase M1 (GSTM1), aryl hydrocarbon receptor (AHR), aryl hydrocarbon receptor nuclear translocator (ARNT) and catechol-O-methyltransferase (COMT) mRNA levels in the mouse liver were measured by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) method. Excluding CYP1A1, experiments revealed significant differences in the expression of these genes between adult- and aged-control animals. The influence of stress on the expression of genes studied was shown to be higher in adult mice than in aged ones. Our results clearly demonstrate the lack of response or even the attenuation of gene expression in aged animals that may play an important role in age-related pathologies and diseases

  7. Genetic and vascular modifiers of age-sensitive cognitive skills: effects of COMT, BDNF, ApoE, and hypertension.

    Science.gov (United States)

    Raz, Naftali; Rodrigue, Karen M; Kennedy, Kristen M; Land, Susan

    2009-01-01

    Several single nucleotide polymorphisms have been linked to neural and cognitive variation in healthy adults. We examined contribution of three polymorphisms frequently associated with individual differences in cognition (Catechol-O-Methyl-Transferase Val158Met, Brain-Derived-Neurotrophic-Factor Val66Met, and Apolipoprotein E epsilon4) and a vascular risk factor (hypertension) in a sample of 189 volunteers (age 18-82). Genotypes were determined from buccal culture samples, and cognitive performance was assessed in 4 age-sensitive domains?fluid intelligence, executive function (inhibition), associative memory, and processing speed. We found that younger age and COMT Met/Met genotype, associated with low COMT activity and higher prefrontal dopamine content, were independently linked to better performance in most of the tested domains. Homozygotes for Val allele of BDNF polymorphism exhibited better associative memory and faster speed of processing than the Met allele carriers, with greater effect for women and persons with hypertension. Carriers of ApoE epsilon4 allele evidenced steeper age-related increase in costs of Stroop color interference, but showed no negative effects on memory. The findings indicate that age-related cognitive performance is differentially affected by distinct genetic factors and their interactions with vascular health status. (c) 2009 APA, all rights reserved.

  8. [Study of genetic variants in the BDNF, COMT, DAT1 and SERT genes in Colombian children with attention deficit disorder].

    Science.gov (United States)

    Ortega-Rojas, Jenny; Arboleda-Bustos, Carlos E; Morales, Luis; Benítez, Bruno A; Beltrán, Diana; Izquierdo, Álvaro; Arboleda, Humberto; Vásquez, Rafael

    Attention deficit and hyperactive disorder (ADHD) is highly prevalent among children in Bogota City. Both genetic and environmental factors play a very important role in the etiology of ADHD. However, to date few studies have addressed the association of genetic variants and ADHD in the Colombian population. To test the genetic association between polymorphisms in the DAT1, HTTLPR, COMT and BDNF genes and ADHD in a sample from Bogota City. We genotyped the most common polymorphisms in DAT1, SERT, COMT and BDNF genes associated with ADHD using conventional PCR followed by restriction fragment length polymorphism (RFLP) in 97 trios recruited in a medical center in Bogota. The transmission disequilibrium test (TDT) was used to determine the association between such genetic variants and ADHD. The TDT analysis showed that no individual allele of any variant studied has a preferential transmission. Our results suggest that the etiology of the ADHD may be complex and involves several genetic factors. Further studies in other candidate polymorphisms in a larger sample size will improve our knowledge of the ADHD in Colombian population. Copyright © 2016 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  9. Comparative evaluation of two radioenzymatic procedures designed to determine noradrenaline in the plasma (COMT assay and PNMT assay)

    International Nuclear Information System (INIS)

    Barth, A.

    1984-01-01

    A comparative evaluation of two radioenzymatic procedures to determine the concentration of noradrenaline in the plasma - with linearity, sensitivity, specifity and accuracy serving as test criteria - led to the following results: In view of a probability of error in the order of 2% both methods were judged to show a satisfactory sensitivity. The specific of the COMT assay, by contrast with that of the PNMT assay, was found to be wanting, as the noradrenaline measurements in the presence of other biogenic amines were biassed in such a way that the values determined were higher than the actual concentrations. During antihypertensive treatment even minimal changes in the noradrenaline concentration can be ascertained on a quantitative basis. If suitable hardware is available, the COMT assay permits up to 25 single determinations to be carried out per day, while the number of double determinations is restricted to 7 per day. One advantage, however, lies in the fact that several catecholamines in the plasma can be detected simultaneously, if required. In cases where the noradrenaline concentration alone is to be determined for clinical purposes, preference should be given to the PNMT assay, as both tests showed equal linearity and sensitivity. (TRV) [de

  10. 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, both at the level of 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. PMID:23278923

  11. 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.

  12. [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.

  13. The role of COMT and plasma proline in the variable penetrance of autistic spectrum symptoms in 22q11.2 deletion syndrome

    NARCIS (Netherlands)

    Hidding, E.; Swaab, H.; de Sonneville, L. M J; van Engeland, H.; Vorstman, J. A S

    2016-01-01

    This paper examines how COMT158 genotypes and plasma proline levels are associated with variable penetrance of social behavioural and social cognitive problems in 22q11.2 deletion syndrome (22q11DS). Severity of autistic spectrum symptoms of 45 participants with 22q11DS was assessed using the Autism

  14. White matter microstructure in 22q11 deletion syndrome: a pilot diffusion tensor imaging and voxel-based morphometry study of children and adolescents.

    Science.gov (United States)

    Sundram, Frederick; Campbell, Linda E; Azuma, Rayna; Daly, Eileen; Bloemen, Oswald J N; Barker, Gareth J; Chitnis, Xavier; Jones, Derek K; van Amelsvoort, Therese; Murphy, Kieran C; Murphy, Declan G M

    2010-06-01

    Young people with 22q11 Deletion Syndrome (22q11DS) are at substantial risk for developing psychosis and have significant differences in white matter (WM) volume. However, there are few in vivo studies of both WM microstructural integrity (as measured using Diffusion Tensor (DT)-MRI) and WM volume in the same individual. We used DT-MRI and structural MRI (sMRI) with voxel based morphometry (VBM) to compare, respectively, the fractional anisotropy (FA) and WM volume of 11 children and adolescents with 22q11DS and 12 controls. Also, within 22q11DS we related differences in WM to severity of schizotypy, and polymorphism of the catechol-O-methyltransferase (COMT) gene. People with 22q11DS had significantly lower FA in inter-hemispheric and brainstem and frontal, parietal and temporal lobe regions after covarying for IQ. Significant WM volumetric increases were found in the internal capsule, anterior brainstem and frontal and occipital lobes. There was a significant negative correlation between increased schizotypy scores and reduced WM FA in the right posterior limb of internal capsule and the right body and left splenium of corpus callosum. Finally, the Val allele of COMT was associated with a significant reduction in both FA and volume of WM in the frontal lobes, cingulum and corpus callosum. Young people with 22q11DS have significant differences in both WM microstructure and volume. Also, there is preliminary evidence that within 22q11DS, some regional differences in FA are associated with allelic variation in COMT and may perhaps also be associated with schizotypy.

  15. Levodopa/carbidopa and entacapone in the treatment of Parkinson’s disease: efficacy, safety and patient preference

    Directory of Open Access Journals (Sweden)

    Thomas Müller

    2009-01-01

    Full Text Available Thomas Müller1,21Department of Neurology, St. Joseph Hospital Berlin-Weißensee, Berlin, Germany; 2IGSN, Ruhr University of Bochum, Bochum, GermanyAbstract: Levodopa (LD is the oldest, most efficacious and best-tolerated drug for dopaminergic substitution of patients with Parkinson’s disease (PD. Its main drawback is its short half-life, which supports onset of motor complications in the long term. Therefore well-informed PD patients mostly accept LD therapy as late as possible. Recent LD trials indicate that a combination of LD with carbidopa (CD and the catechol-O-methyltransferase (COMT inhibitor entacapone (EN may reduce the onset of these motor complications to a certain extent. This observation is further supported by pharmacokinetic trials and experimental research, but there is still a need to confirm this in a clinical trial, which is under way. Additionally, combined LD/CD/EN was superior to LD/CD administration regarding cognition, muscle behavior and gastrointestinal function in small clinical trials. Moreover there is accumulating evidence that combined COMT inhibition with LD administration reduces homocysteine synthesis. In the long term, homocysteine elevation supports onset of arteriosclerosis-related disorders, which are more frequent in PD patients according to epidemiological studies than in the normal healthy population. The introduction of LD/CD/EN in one tablet supported patients’ preference of COMT inhibition as an essential component of LD/DDI therapy, as this combination reduced number and size of tablets.Keywords: levodopa, entacapone, Parkinson’s disease, preference, compliance, acceptance

  16. 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

    Directory of Open Access Journals (Sweden)

    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

  17. COMT Val158Met and 5-HT1A-R -1019 C/G polymorphisms: effects on the negative symptom response to clozapine.

    Science.gov (United States)

    Bosia, Marta; Lorenzi, Cristina; Pirovano, Adele; Guglielmino, Carmelo; Cocchi, Federica; Spangaro, Marco; Bramanti, Placido; Smeraldi, Enrico; Cavallaro, Roberto

    2015-01-01

    Clozapine is still considered the gold standard for treatment-resistant schizophrenia patients; however, up to 40% of patients do not respond adequately. Identifying potential predictors of clinical response to this last-line antipsychotic could represent an important goal for treatment. Among these, functional polymorphisms involved in dopamine system modulation, known to be disrupted in schizophrenia, may play a role. We examined the COMT Val158Met polymorphism, which plays a key role in dopamine regulation at the prefrontal level, and the 5-HT1A-R -1019 C/G polymorphism, a target of clozapine activity involved in the interaction between the serotonin and dopamine systems. 107 neuroleptic-refractory, biologically unrelated Italian patients (70 males and 37 females) with a DSM-IV diagnosis of schizophrenia who were being treated with clozapine were recruited. Psychopathology was assessed by the Positive and Negative Symptoms Scale (PANSS) at the beginning of treatment, and at weeks 8 and 12. Genomic DNA was extracted from venous blood samples. COMT rs4680 (Val158Met) and 5-HT1A-R rs6295 (-1019 C/G) polymorphisms were analyzed by PCR-based restriction fragment length and direct sequencing, respectively. We found a significant effect of COMT and 5-HT1A-R on the PANSS Negative Subscale variation, with greater improvement among COMT Val/Val and 5-HT1A-R G/G subjects. The findings support the hypothesis that COMT rs4680 and 5-HT1A-R rs6295 polymorphisms could influence the negative symptom response to clozapine, probably through modulation of the dopaminergic system.

  18. A Multi-scale Computational Platform to Mechanistically Assess the Effect of Genetic Variation on Drug Responses in Human Erythrocyte Metabolism.

    Science.gov (United States)

    Mih, Nathan; Brunk, Elizabeth; Bordbar, Aarash; Palsson, Bernhard O

    2016-07-01

    Progress in systems medicine brings promise to addressing patient heterogeneity and individualized therapies. Recently, genome-scale models of metabolism have been shown to provide insight into the mechanistic link between drug therapies and systems-level off-target effects while being expanded to explicitly include the three-dimensional structure of proteins. The integration of these molecular-level details, such as the physical, structural, and dynamical properties of proteins, notably expands the computational description of biochemical network-level properties and the possibility of understanding and predicting whole cell phenotypes. In this study, we present a multi-scale modeling framework that describes biological processes which range in scale from atomistic details to an entire metabolic network. Using this approach, we can understand how genetic variation, which impacts the structure and reactivity of a protein, influences both native and drug-induced metabolic states. As a proof-of-concept, we study three enzymes (catechol-O-methyltransferase, glucose-6-phosphate dehydrogenase, and glyceraldehyde-3-phosphate dehydrogenase) and their respective genetic variants which have clinically relevant associations. Using all-atom molecular dynamic simulations enables the sampling of long timescale conformational dynamics of the proteins (and their mutant variants) in complex with their respective native metabolites or drug molecules. We find that changes in a protein's structure due to a mutation influences protein binding affinity to metabolites and/or drug molecules, and inflicts large-scale changes in metabolism.

  19. A Multi-scale Computational Platform to Mechanistically Assess the Effect of Genetic Variation on Drug Responses in Human Erythrocyte Metabolism.

    Directory of Open Access Journals (Sweden)

    Nathan Mih

    2016-07-01

    Full Text Available Progress in systems medicine brings promise to addressing patient heterogeneity and individualized therapies. Recently, genome-scale models of metabolism have been shown to provide insight into the mechanistic link between drug therapies and systems-level off-target effects while being expanded to explicitly include the three-dimensional structure of proteins. The integration of these molecular-level details, such as the physical, structural, and dynamical properties of proteins, notably expands the computational description of biochemical network-level properties and the possibility of understanding and predicting whole cell phenotypes. In this study, we present a multi-scale modeling framework that describes biological processes which range in scale from atomistic details to an entire metabolic network. Using this approach, we can understand how genetic variation, which impacts the structure and reactivity of a protein, influences both native and drug-induced metabolic states. As a proof-of-concept, we study three enzymes (catechol-O-methyltransferase, glucose-6-phosphate dehydrogenase, and glyceraldehyde-3-phosphate dehydrogenase and their respective genetic variants which have clinically relevant associations. Using all-atom molecular dynamic simulations enables the sampling of long timescale conformational dynamics of the proteins (and their mutant variants in complex with their respective native metabolites or drug molecules. We find that changes in a protein's structure due to a mutation influences protein binding affinity to metabolites and/or drug molecules, and inflicts large-scale changes in metabolism.

  20. 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...

  1. Effects of COMT, DRD2, BDNF, and APOE Genotypic Variation on Treatment Efficacy and Cognitive Side Effects of Electroconvulsive Therapy.

    Science.gov (United States)

    Bousman, Chad A; Katalinic, Natalie; Martin, Donel M; Smith, Deidre J; Ingram, Anna; Dowling, Nathan; Ng, Chee; Loo, Colleen K

    2015-06-01

    The aim of this study was to explore the main and interaction effects of the COMT Val158Met, DRD2 C957T, BDNF Val66Met, and APOE polymorphisms on treatment efficacy and cognitive side effects of electroconvulsive therapy (ECT). A total of 117 adult inpatients with a diagnosis of major depressive disorder recruited from 3 hospitals were administered the Montgomery-Äsberg Depression Rating Scale and a cognitive battery assessing global cognition, anterograde memory, executive function, speed and concentration, as well as retrograde memory at baseline and after ECT treatment. DRD2 C957T heterozygotes had 3.7 (95% confidence interval, 1.13-12.25; P = 0.032) greater odds of remission compared with CC homozygotes. Among the men, COMT Val/Val carriers had greater depressive symptom reduction compared with Met/Met carriers (Montgomery-Äsberg Depression Rating Scale percentage of reduction, 76% vs 35%; P = 0.020) but not among the women (P = 0.903) after ECT. For cognitive outcomes, an interaction effect on anterograde memory was observed between the DRD2 and BDNF polymorphisms (P = 0.016), in which carriers of the DRD2 TT and BDNF Val/Val genotypes had significantly less decline in anterograde performance than those that carried the TC and Met-allele (P = 0.001) or CC and Met-allele (P = 0.003) genotypes. However, no results withstood correction for multiple comparisons. These observations provide preliminary evidence supporting an association between common functional genotypic variation and ECT efficacy as well as anterograde memory side effects after ECT. Validation of these findings is required before firm conclusions can be made and clinical utility can be assessed.

  2. Association of COMT and PRODH gene variants with intelligence quotient (IQ) and executive functions in 22q11.2DS subjects.

    Science.gov (United States)

    Carmel, Miri; Zarchi, Omer; Michaelovsky, Elena; Frisch, Amos; Patya, Miriam; Green, Tamar; Gothelf, Doron; Weizman, Abraham

    2014-09-01

    The 22q11.2 deletion syndrome (22q11.2DS) carries the highest genetic risk factor for the development of schizophrenia. We investigated the association of genetic variants in two schizophrenia candidate genes with executive function (EF) and IQ in 22q11.2DS individuals. Ninety two individuals with 22q11.2 deletion were studied for the genetic association between COMT and PRODH variants and EF and IQ. Subjects were divided into children (under 12 years old), adolescents (between 12 and 18 years old) and adults (older than 18 years), and genotyped for the COMT Val158Met (rs4680) and PRODH Arg185Trp (rs4819756) polymorphisms. The participants underwent psychiatric evaluation and EF assessment. Our main finding is a significant influence of the COMT Val158Met polymorphism on both IQ and EF performance. Specifically, 22q11.2DS subjects with Met allele displayed higher IQ scores in all age groups compared to Val carriers, reaching significance in both adolescents and adults. The Met allele carriers performed better than Val carriers in EF tasks, being statistically significant in the adult group. PRODH Arg185Trp variant did not affect IQ or EF in our 22q11.2DS cohort. In conclusion, functional COMT variant, but not PRODH, affects IQ and EF in 22q11.2DS subjects during neurodevelopment with a maximal effect at adulthood. Future studies should monitor the cognitive performance of the same individuals from childhood to old age. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Genetic Predisposition to Poor Opioid Response in Preterm Infants: Impact of KCNJ6 and COMT Polymorphisms on Pain Relief After Endotracheal Intubation.

    Science.gov (United States)

    Elens, Laure; Norman, Elisabeth; Matic, Maja; Rane, Anders; Fellman, Vineta; van Schaik, Ron H N

    2016-08-01

    Single-nucleotide polymorphisms in genes involved in pain control might predispose to exaggerated sensitivity or difference in opioid analgesic effect. The relevance of the KCNJ6 -1250G>A (rs6517442, c.-1787G>A) and the catecholamine-O-methyltransferase (COMT) c.472G>A (rs4680, ValMet) single-nucleotide polymorphisms were studied in preterm infants needing intubation and randomized to a premedication strategy including remifentanil (n = 17) or morphine (n = 17). Pain was scored with Astrid Lindgren and Lund Children's Hospital Pain Assessment Scale every 30 minutes for 6 hours. The pain relief provided by the opioids was compared between the different KCNJ6 and COMT genotypes. Infants homozygous for the KCNJ6 -1250A allele had an increased duration after intubation to achieve a score indicating no pain compared with infants with the A/G or G/G genotypes (182 ± 30, 109 ± 29, and 60 ± 21 minutes, respectively; Logrank = 7.5, P = 0.006). Similarly, the duration was increased in individuals with the COMT Val/Val alleles compared with Val/Met and Met/Met (285 ± 37, 137 ± 25, and 63 ± 15 minutes, respectively; Logrank = 14.4, P = 0.0021). Cox proportional hazards analysis confirmed that the variation in both genes was independently associated with susceptibility to respond to therapy. We conclude that the KCNJ6 -1250A and COMT Val alleles are predisposing preterm newborns to diminished opioid-induced pain relief.

  4. The COMT Val158 Met polymorphism as an associated risk factor for Alzheimer disease and mild cognitive impairment in APOE 4 carriers

    Directory of Open Access Journals (Sweden)

    Borda Sandra

    2009-09-01

    Full Text Available Abstract Background The aim of this study is to examine the influence of the catechol-O-methyltranferase (COMT gene (polymorphism Val158 Met as a risk factor for Alzheimer's disease (AD and mild cognitive impairment of amnesic type (MCI, and its synergistic effect with the apolipoprotein E gene (APOE. A total of 223 MCI patients, 345 AD and 253 healthy controls were analyzed. Clinical criteria and neuropsychological tests were used to establish diagnostic groups. The DNA Bank of the University of the Basque Country (UPV-EHU (Spain determined COMT Val158 Met and APOE genotypes using real time polymerase chain reaction (rtPCR and polymerase chain reaction (PCR, and restriction fragment length polymorphism (RFLPs, respectively. Multinomial logistic regression models were used to determine the risk of AD and MCI. Results Neither COMT alleles nor genotypes were independent risk factors for AD or MCI. The high activity genotypes (GG and AG showed a synergistic effect with APOE ε4 allele, increasing the risk of AD (OR = 5.96, 95%CI 2.74-12.94, p In MCI patients such as synergistic effect was only found between AG and APOE ε4 allele (OR = 3.21 95%CI 1.56-6.63, p = 0.02 and was greater in men (OR = 5.88 95%CI 1.69-20.42, p Conclusion COMT (Val158 Met polymorphism is not an independent risk factor for AD or MCI, but shows a synergistic effect with APOE ε4 allele that proves greater in women with AD.

  5. 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. Copyright © 2012 Wiley Periodicals, Inc.

  6. Value of preapproval safety data in predicting postapproval hepatic safety and assessing the legitimacy of class warning.

    Science.gov (United States)

    Lin, Yeong-Liang; Wu, Ya-Chi; Gau, Churn-Shiouh; Lin, Min-Shung

    2012-02-01

    The objective of this study was to systematically evaluate whether preapproval safety data for nonhepatotoxic drugs and hepatotoxic drugs can be compared to improve preapproval prediction of postapproval hepatic safety and to assess the legitimacy of applying class warnings. Drugs within a therapeutic class that included at least one drug that had been withdrawn from the market because of liver toxicity or had a warning of potential liver toxicity issued by major regulatory agencies, and at least one drug free from such regulatory action, were identified and divided into two groups: drugs with and drugs without regulatory action. Preapproval clinical data [including the elevation rates of alanine aminotransferse (ALT) and withdrawal due to liver toxicity, the number of patients with combined elevation of ALT and bilirubin, and liver failure] and nonclinical data (including chemical structures, metabolic pathways, and other significant findings in animal studies) were compared between the two groups. Six drug classes were assessed in this study: thiazolidinediones, cyclooxygenase-2 inhibitors, fluoroquinolones, catechol-O-methyltransferase (COMT) inhibitors, leukotriene receptor inhibitors, and endothelin receptor antagonists. In two classes (COMT inhibitors and endothelin receptor antagonists), drugs with regulatory action had significantly higher rates of ALT elevation of more than threefold and greater numbers of patients with combined elevation of ALT and bilirubin than drugs without regulatory action. Drugs with regulatory action also had chemical structures or metabolic pathways associated with the toxicity. The legitimacy of class warnings was refuted in all six classes of drugs. Preapproval safety data may help predict postapproval hepatic safety and can be used to assess the legitimacy of applying class warnings.

  7. Right inferior frontal cortex activity correlates with tolcapone responsivity in problem and pathological gamblers

    Directory of Open Access Journals (Sweden)

    Andrew S. Kayser

    2017-01-01

    Full Text Available Failures of self-regulation in problem and pathological gambling (PPG are thought to emerge from failures of top-down control, reflected neurophysiologically in a reduced capacity of prefrontal cortex to influence activity within subcortical structures. In patients with addictions, these impairments have been argued to alter evaluation of reward within dopaminergic neuromodulatory systems. Previously we demonstrated that augmenting dopamine tone in frontal cortex via use of tolcapone, an inhibitor of the dopamine-degrading enzyme catechol-O-methyltransferase (COMT, reduced delay discounting, a measure of impulsivity, in healthy subjects. To evaluate this potentially translational approach to augmenting prefrontal inhibitory control, here we hypothesized that increasing cortical dopamine tone would reduce delay discounting in PPG subjects in proportion to its ability to augment top-down control. To causally test this hypothesis, we administered the COMT inhibitor tolcapone in a randomized, double-blind, placebo-controlled, within-subject study of 17 PPG subjects who performed a delay discounting task while functional MRI images were obtained. In this subject population, we found that greater BOLD activity during the placebo condition within the right inferior frontal cortex (RIFC, a region thought to be important for inhibitory control, correlated with greater declines in impulsivity on tolcapone versus placebo. Intriguingly, connectivity between RIFC and the right striatum, and not the level of activity within RIFC itself, increased on tolcapone versus placebo. Together, these findings support the hypothesis that tolcapone-mediated increases in top-down control may reduce impulsivity in PPG subjects, a finding with potential translational relevance for gambling disorders, and for behavioral addictions in general.

  8. Dopaminergic influences on executive function and impulsive behaviour in impulse control disorders in Parkinson's disease.

    Science.gov (United States)

    Leroi, Iracema; Barraclough, Michelle; McKie, Shane; Hinvest, Neal; Evans, Jonathan; Elliott, Rebecca; McDonald, Kathryn

    2013-09-01

    The development of impulse control disorders (ICDs) in Parkinson's disease (PD) may arise from an interaction among cognitive impairment, impulsive responding and dopaminergic state. Dopaminergic state may be influenced by pharmacologic or genotypic (catechol-O-methyltransferase; COMT) factors. We sought to investigate this interaction further by comparing those with (n = 35) and without (n = 55) ICDs on delay-discounting in different pharmacologic conditions (ON or OFF dopaminergic medication) and on response inhibition as well as aspects of executive functioning in the ON state. We then undertook an exploratory sub-group analysis of these same tasks when the overall PD group was divided into different allelic variants of COMT (val/val vs. met/met). A healthy control group (HC; n = 20) was also included. We found that in those with PD and ICDs, 'cognitive flexibility' (set shifting, verbal fluency, and attention) in the ON medication state was not impaired compared with those without ICDs. In contrast, our working memory, or 'cognitive focus', task was impaired in both PD groups compared with the HC group when ON. During the delay-discounting task, the PD with ICDs group expressed greater impulsive choice compared with the PD group without ICDs, when in the ON, but not the OFF, medication state. However, no group difference on the response inhibition task was seen when ON. Finally, the met homozygous group performed differently on tests of executive function compared with the val homozygous group. We concluded that the disparity in levels of impairment among different domains of executive function and impulsive decision-making distinguishes those with ICD in PD from those without ICD, and may in part be affected by dopaminergic status. Both pharmacologic and genotypic influences on dopaminergic state may be important in ICD. © 2013 The British Psychological Society.

  9. Capture compound mass spectrometry sheds light on the molecular mechanisms of liver toxicity of two Parkinson drugs.

    Science.gov (United States)

    Fischer, Jenny J; Michaelis, Simon; Schrey, Anna K; Graebner, Olivia Graebner nee; Glinski, Mirko; Dreger, Mathias; Kroll, Friedrich; Koester, Hubert

    2010-01-01

    Capture compound mass spectrometry (CCMS) is a novel technology that helps understand the molecular mechanism of the mode of action of small molecules. The Capture Compounds are trifunctional probes: A selectivity function (the drug) interacts with the proteins in a biological sample, a reactivity function (phenylazide) irreversibly forms a covalent bond, and a sorting function (biotin) allows the captured protein(s) to be isolated for mass spectrometric analysis. Tolcapone and entacapone are potent inhibitors of catechol-O-methyltransferase (COMT) for the treatment of Parkinson's disease. We aimed to understand the molecular basis of the difference of both drugs with respect to side effects. Using Capture Compounds with these drugs as selectivity functions, we were able to unambiguously and reproducibly isolate and identify their known target COMT. Tolcapone Capture Compounds captured five times more proteins than entacapone Capture Compounds. Moreover, tolcapone Capture Compounds isolated mitochondrial and peroxisomal proteins. The major tolcapone-protein interactions occurred with components of the respiratory chain and of the fatty acid beta-oxidation. Previously reported symptoms in tolcapone-treated rats suggested that tolcapone might act as decoupling reagent of the respiratory chain (Haasio et al., 2002b). Our results demonstrate that CCMS is an effective tool for the identification of a drug's potential off targets. It fills a gap in currently used in vitro screens for drug profiling that do not contain all the toxicologically relevant proteins. Thereby, CCMS has the potential to fill a technological need in drug safety assessment and helps reengineer or to reject drugs at an early preclinical stage.

  10. 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.

  11. Methanization in Burgundy-Franche-Comte - Figures and benchmarks. Agricultural methanization in Franche-Comte - Reflection guide for projects. Methanization development in Burgundy - Assessment 2014. Biogas sector in Burgundy. Methanization development in Burgundy - How to develop a project in Burgundy

    International Nuclear Information System (INIS)

    Aucordonnier, Bertrand; SIBUE, Lionel; Granger, Sylvie; Pervenchon, Frank; Forgue, Isabelle; Lirzin, Frank; Aucordonnier, Bertand; Abrahamse, Philippe; Dondaine, Regis; Rousseau, Christophe; Fevre, Jean-Michel; Carbonnier, Arnaud; Gontier, Thomas; Lemaire, Sylvie; Gallois, Vincent; Lachaize, M.

    2015-03-01

    A first document proposes graphs, figures and maps which illustrate various aspects of the situation and development of methanization in France and in the Burgundy-Franche-Comte region (number and location of installations, production evolution, biomass origins, biogas valorisation). A second document presents methanization (basic principles, process types, valorisation), describes agricultural methanization (substrate origin, use of final energy, use of digestates) and proposes elements of thought for methanization development regarding waste origin, project definition, various concerns (energy, environment, agriculture), digestate use and quantities, methane use, and installation sizing. A publication then proposes a synthetic overview of methanization development in Burgundy: number of supported projects, installations (evolution of their number, used materials, production), and support activities. The next publication proposes an assessment and an overview of the biogas sector in Burgundy: presentation and recommendations, assessment in terms of jobs, activities and expertise, professional education and training. The last document recalls some elements related to the methanization technique, outlines some important issues (materials, valorisation type for biogas and for digestate) to be addressed for an agricultural methanization project, and evokes benefits of methanization and some economic aspects. It also briefly describes how to start a project in the region

  12. 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.

  13. Pre-travel consultation: evaluation of primary care physician practice in the Franche-Comté region.

    Science.gov (United States)

    Piotte, Emeline; Bellanger, Anne-Pauline; Piton, Gaël; Millon, Laurence; Marguet, Philippe

    2013-01-01

    Primary care physicians (PCP) are first in line to provide adequate pre-travel medical advice. Little data are available on the content of pre-travel PCP consultations in France. We undertook an observational survey to assess the level of specific knowledge among PCPs on health advice, vaccinations, and malaria prophylaxis. Standardized questionnaires were sent to a random sample of 400 PCPs practicing in the Franche-Comté regions (eastern France) who were asked to complete and return it on a voluntary and anonymous basis. The questionnaire requested sociodemographic details, practice-related characteristics, and proposed three clinical situations with multiple choice questions (MCQ). To identify factors associated with a higher level of specific knowledge in travel medicine, results were studied by uni- and multivariate analyses. An overall score was calculated based on the MCQ answers and a motivation score was calculated based on parameters such as frequency and developments in pre-travel consulting at the practice, PCPs' personal experience as travelers, and the formal agreement of PCPs to administer yellow fever vaccination. The response rate was 37.5%, with 150 questionnaires returned completed and suitable for analysis. After multivariate logistic regression, the three variables associated with a higher score were: proximity of a vaccination center (p = 0.001), motivation score (p = 0.004), and absence of request for expert advice on malaria prophylaxis (p = 0.007). PCPs play an important role in travel medicine. This study showed that their high level of knowledge in travel medicine was mostly linked to their motivation to practice in this specialized discipline. © 2013 International Society of Travel Medicine.

  14. Psychophysiological traits of men with several genotypes in polymorphic locus Val158Met COMT and different levels of aggressiveness

    Directory of Open Access Journals (Sweden)

    Pavel N. Ermakov

    2018-03-01

    Full Text Available Background. The catechol-O-methyl transferase gene influences the reuptake of monoamines (dopamine, serotonin, noradrenaline from the synaptic space. The structural peculiarities of this gene are linked with the duration of stay of neurotransmitters in the synaptic gap and the emergence and duration of emotional reactions, which may considerably affect a person’s level of aggressiveness; these peculiarities may manifest as psychophysiological characteristics. Objective and design. This study investigated the amplitude, spatio-temporal traits and sources of evoked brain activity in men with several genotypes in the polymorphic locus Val158Met in the COMT (Catechol-O-methyl transferase gene, levels of aggressiveness using the Buss-Darkee inventory, proneness to various types of deviant and addictive behaviors in accordance with the methods of A.N. Oryol and the preferred strategies of behavior during conflict in accordance with the methods of Kenneth Thomas. Statistical processing of psychodiagnostic data included dispersive (ANOVA and discriminative analyses. Results. This study found significant differences in the parameters of evoked brain activity components in responses to emotionally charged stimuli (“aggression”, “positive”, “tolerance”, “extremism, terrorism” compared with neutral images. Student’s t-test (Holms- corrected for multiple comparisons was used to analyze the EEG-VEP data. Conclusion. This study confirmed the hypothesis of differences in spatio-temporal and amplitude parameters of evoked brain potentials in young men exhibiting differing levels of aggressiveness. The sources of evoked brain activity determined using sLORETA (Standardized Low-resolution Brain Electromagnetic Tomography were different between carriers of different genotypes.

  15. Lower baseline performance but greater plasticity of working memory for carriers of the val allele of the COMT Val¹⁵⁸Met polymorphism.

    Science.gov (United States)

    Bellander, Martin; Bäckman, Lars; Liu, Tian; Schjeide, Brit-Maren M; Bertram, Lars; Schmiedek, Florian; Lindenberger, Ulman; Lövdén, Martin

    2015-03-01

    Little is known about genetic contributions to individual differences in cognitive plasticity. Given that the neurotransmitter dopamine is critical for cognition and associated with cognitive plasticity, we investigated the effects of 3 polymorphisms of dopamine-related genes (LMX1A, DRD2, COMT) on baseline performance and plasticity of working memory (WM), perceptual speed, and reasoning. One hundred one younger and 103 older adults underwent approximately 100 days of cognitive training, and extensive testing before and after training. We analyzed the baseline and posttest data using latent change score models. For working memory, carriers of the val allele of the COMT polymorphism had lower baseline performance and larger performance gains from training than carriers of the met allele. There was no significant effect of the other genes or on other cognitive domains. We relate this result to available evidence indicating that met carriers perform better than val carriers in WM tasks taxing maintenance, whereas val carriers perform better at updating tasks. We suggest that val carriers may show larger training gains because updating operations carry greater potential for plasticity than maintenance operations. PsycINFO Database Record (c) 2015 APA, all rights reserved.

  16. [Assessment of 10 years of memory consultations in the Franche-Comté: Description and analysis of the RAPID regional database].

    Science.gov (United States)

    Bereau, M; Sylvestre, G; Mauny, F; Puyraveau, M; Baudier, F; Magnin, E; Berger, E; Vandel, P; Galmiche, J; Chopard, G

    2015-09-01

    The aim of this study was to evaluate the impact, on a regional scale (Franche-Comté), of 3 National Alzheimer care plans, particularly concerning the development of the offer of care management by clinicians as well as the panel of diagnoses concerned. Data on sociodemographic, neuropsychological and diagnostic characteristics were retrieved from the RAPID regional database between 1st January 2003 and 31st December 2012. These analyses focused exclusively on patients who had an initial consultation (n=12,017) during the same period. The existence of a previously established health network capable of carrying out governmental health plans has produced an effective interface between regional administrative structures responsible for the implementation of these plans and health professionals responsible for carrying out them out. This network study, the use of a battery of tests and a common software database have enabled the development of patient care management throughout the Franche-Comté region. It also showed the diversification of diagnoses mentioned over the past years as well as changes in clinical practices on how to address the issue of cognitive impairment. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  17. 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. © 2016 Wiley Periodicals, Inc.

  18. Parkinson’s Disease: From Pathogenesis to Pharmacogenomics

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    Ramón Cacabelos

    2017-03-01

    Full Text Available Parkinson’s disease (PD is the second most important age-related neurodegenerative disorder in developed societies, after Alzheimer’s disease, with a prevalence ranging from 41 per 100,000 in the fourth decade of life to over 1900 per 100,000 in people over 80 years of age. As a movement disorder, the PD phenotype is characterized by rigidity, resting tremor, and bradykinesia. Parkinson’s disease -related neurodegeneration is likely to occur several decades before the onset of the motor symptoms. Potential risk factors include environmental toxins, drugs, pesticides, brain microtrauma, focal cerebrovascular damage, and genomic defects. Parkinson’s disease neuropathology is characterized by a selective loss of dopaminergic neurons in the substantia nigra pars compacta, with widespread involvement of other central nervous system (CNS structures and peripheral tissues. Pathogenic mechanisms associated with genomic, epigenetic and environmental factors lead to conformational changes and deposits of key proteins due to abnormalities in the ubiquitin–proteasome system together with dysregulation of mitochondrial function and oxidative stress. Conventional pharmacological treatments for PD are dopamine precursors (levodopa, l-DOPA, l-3,4 dihidroxifenilalanina, and other symptomatic treatments including dopamine agonists (amantadine, apomorphine, bromocriptine, cabergoline, lisuride, pergolide, pramipexole, ropinirole, rotigotine, monoamine oxidase (MAO inhibitors (selegiline, rasagiline, and catechol-O-methyltransferase (COMT inhibitors (entacapone, tolcapone. The chronic administration of antiparkinsonian drugs currently induces the “wearing-off phenomenon”, with additional psychomotor and autonomic complications. In order to minimize these clinical complications, novel compounds have been developed. Novel drugs and bioproducts for the treatment of PD should address dopaminergic neuroprotection to reduce premature neurodegeneration in

  19. The impact of methylphenidate and its enantiomers on dopamine synthesis and metabolism in vitro.

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    Bartl, Jasmin; Palazzesi, Ferruccio; Parrinello, Michele; Hommers, Leif; Riederer, Peter; Walitza, Susanne; Grünblatt, Edna

    2017-10-03

    Methylphenidate (MPH), a psychostimulant, is an effective first-line treatment for the symptoms associated with Attention-Deficit/Hyperactivity Disorder (ADHD). Although most MPH formulations are composed of the racemic 1:1 mixture of the two enantiomers (d- and l-threo), converging lines of evidence indicate that d-threo MPH seems to be superior to the l-isomer. We aimed to investigate whether MPH racemic mixture or pure enantiomers influence the enzyme activity of tyrosine hydroxylase (TH), monoamine oxidase B (MAO-B), catechol-O-methyltransferase (COMT), and aldehyde dehydrogenase (ALDH) in vitro in homogenates of rat PC12 cells incubated with racemic, d- and l-threo MPH (1nM up to 100μM), or a vehicle for control. We could observe dose dependent enhancement of TH activity with d-threo MPH, probably due to its higher affinity to the enzyme, which we could confirm for d-threo versus l-threo MPH via docking and molecular dynamic simulations analysis. MAO-B enzyme activity was found to be enhanced when incubated with both d- and l-isomers but not with the racemic mixture. This conflicting result was hypothesized to be due to possible aggregation of the two enantiomers or other molecular conformations. Such a possible interaction was observed indirectly, when TH was incubated with constant d-threo MPH while increasing l-isomer (increasing total MPH concentrations). Hence, TH activity was slightly decreased with increased l-isomer. In conclusion, the current in vitro investigation points to the stereoselectivity of the investigated enzymes and pharmacological effects of MPH enantiomers. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Genetic polymorphisms in monoamine systems and outcome of cognitive behavior therapy for social anxiety disorder.

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    Evelyn Andersson

    Full Text Available 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.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.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.None of the three gene variants, 5-HTTLPR, COMTval158met and TPH2 G-703T, was associated with long-term response to CBT for SAD.ClinicalTrials.gov (ID-NCT0056496.

  1. Gene expression profiling in the striatum of inbred mouse strains with distinct opioid-related phenotypes

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    Piechota Marcin

    2006-06-01

    Full Text Available Abstract Background Mouse strains with a contrasting response to morphine provide a unique model for studying the genetically determined diversity of sensitivity to opioid reward, tolerance and dependence. Four inbred strains selected for this study exhibit the most distinct opioid-related phenotypes. C57BL/6J and DBA/2J mice show remarkable differences in morphine-induced antinociception, self-administration and locomotor activity. 129P3/J mice display low morphine tolerance and dependence in contrast to high sensitivity to precipitated withdrawal observed in SWR/J and C57BL/6J strains. In this study, we attempted to investigate the relationships between genetic background and basal gene expression profile in the striatum, a brain region involved in the mechanism of opioid action. Results Gene expression was studied by Affymetrix Mouse Genome 430v2.0 arrays with probes for over 39.000 transcripts. Analysis of variance with the control for false discovery rate (q Khdrbs1 and ATPase Na+/K+ alpha2 subunit (Atp1a2 with morphine self-administration and analgesic effects, respectively. Finally, the examination of transcript structure demonstrated a possible inter-strain variability of expressed mRNA forms as for example the catechol-O-methyltransferase (Comt gene. Conclusion The presented study led to the recognition of differences in the gene expression that may account for distinct phenotypes. Moreover, results indicate strong contribution of genetic background to differences in gene transcription in the mouse striatum. The genes identified in this work constitute promising candidates for further animal studies and for translational genetic studies in the field of addictive and analgesic properties of opioids.

  2. Who gets afraid in the MRI-scanner? Neurogenetics of state-anxiety changes during an fMRI experiment.

    Science.gov (United States)

    Mutschler, Isabella; Wieckhorst, Birgit; Meyer, Andrea H; Schweizer, Tina; Klarhöfer, Markus; Wilhelm, Frank H; Seifritz, Erich; Ball, Tonio

    2014-11-07

    Experiments using functional magnetic resonance imaging (fMRI) play a fundamental role in affective neuroscience. When placed in an MR scanner, some volunteers feel safe and relaxed in this situation, while others experience uneasiness and fear. Little is known about the basis and consequences of such inter-individually different responses to the general experimental fMRI setting. In this study emotional stimuli were presented during fMRI and subjects' state-anxiety was assessed at the onset and end of the experiment while they were within the scanner. We show that Val/Val but neither Met/Met nor Val/Met carriers of the catechol-O-methyltransferase (COMT) Val(158)Met polymorphism-a prime candidate for anxiety vulnerability-became significantly more anxious during the fMRI experiment (N=97 females: 24 Val/Val, 51 Val/Met, and 22 Met/Met). Met carriers demonstrated brain responses with increased stability over time in the right parietal cortex and significantly better cognitive performances likely mediated by lower levels of anxiety. Val/Val, Val/Met and Met/Met did not significantly differ in state-anxiety at the beginning of the experiment. The exposure of a control group (N=56 females) to the same experiment outside the scanner did not cause a significant increase in state-anxiety, suggesting that the increase we observe in the fMRI experiment may be specific to the fMRI setting. Our findings reveal that genetics may play an important role in shaping inter-individual different emotional, cognitive and neuronal responses during fMRI experiments. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Emotional disorders induced by Hemopressin and RVD-hemopressin(α) administration in rats.

    Science.gov (United States)

    Leone, Sheila; Recinella, Lucia; Chiavaroli, Annalisa; Martinotti, Sara; Ferrante, Claudio; Mollica, Adriano; Macedonio, Giorgia; Stefanucci, Azzurra; Dvorácskó, Szabolcs; Tömböly, Csaba; De Petrocellis, Luciano; Vacca, Michele; Brunetti, Luigi; Orlando, Giustino

    2017-12-01

    The endocannabinoid (eCB) system plays an important role in regulating emotional disorders, and is involved, directly or indirectly, in psychiatric diseases, such as anxiety and depression. Hemopressin, a hemoglobin α chain-derived peptide, and RVD-hemopressin(α), a N-terminally extended form of hemopressin, act as antagonist/inverse agonist and negative allosteric modulator of the cannabinoid 1 (CB1) receptor, respectively. Considering the possible involvement of these peptides on emotional behaviour, the aim of our study was to investigate the behavioural effects of a single intraperitoneal (ip) injection of hemopressin (0.05mg/kg) and RVD-hemopressin(α) (0.05mg/kg), using a series of validated behavioural tests (locomotor activity/open field test, light-dark exploration test, forced swim test) in rats. Prefrontal cortex levels of norepinephrine (NE), dopamine (DA) and serotonin (5-hydroxytryptamine, 5-HT) and the gene expression of monoamine oxidase (MAO-B) and catechol-O-methyltransferase (COMT) were measured by high performance liquid chromatography (HPLC) analysis and real-time reverse transcription polymerase chain reaction (RT-PCR), respectively. Hemopressin administration induced anxiogenic and depressive behaviour, decreased monoamine steady state levels in prefrontal cortex, and increased the gene expression of the enzymes involved in their catabolism. By contrast, RVD- hemopressin(α) induced anxiolytic and antidepressive effects, increased monoamines and decreased the enzymes in prefrontal cortex. In conclusion, in the present study we demonstrated behavioral effects induced by peripheral hemopressin and RVD-hemopressin(α) injections, that could involve modulatory effects on monoaminergic signaling, in the prefrontal cortex. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  4. Influence of Dopamine-Related Genes on Neurobehavioral Recovery after Traumatic Brain Injury during Early Childhood.

    Science.gov (United States)

    Treble-Barna, Amery; Wade, Shari L; Martin, Lisa J; Pilipenko, Valentina; Yeates, Keith Owen; Taylor, H Gerry; Kurowski, Brad G

    2017-06-01

    The present study examined the association of dopamine-related genes with short- and long-term neurobehavioral recovery, as well as neurobehavioral recovery trajectories over time, in children who had sustained early childhood traumatic brain injuries (TBI) relative to children who had sustained orthopedic injuries (OI). Participants were recruited from a prospective, longitudinal study evaluating outcomes of children who sustained a TBI (n = 68) or OI (n = 72) between the ages of 3 and 7 years. Parents completed ratings of child executive function and behavior at the immediate post-acute period (0-3 months after injury); 6, 12, and 18 months after injury; and an average of 3.5 and 7 years after injury. Thirty-two single nucleotide polymorphisms (SNPs) in dopamine-related genes (dopamine receptor D2 [DRD2], solute carrier family 6 member 3 [SLC6A3], solute carrier family 18 member A2 [SLC18A2], catechol-o-methyltransferase [COMT], and ankyrin repeat and kinase domain containing 1 [ANKK1]) were examined in association with short- and long-term executive function and behavioral adjustment, as well as their trajectories over time. After controlling for premorbid child functioning, genetic variation within the SLC6A3 (rs464049 and rs460000) gene was differentially associated with neurobehavioral recovery trajectories over time following TBI relative to OI, with rs464049 surviving multiple testing corrections. In addition, genetic variation within the ANKK1 (rs1800497 and rs2734849) and SLC6A3 (rs464049, rs460000, and rs1042098) genes was differentially associated with short- and long-term neurobehavioral recovery following TBI, with rs460000 and rs464049 surviving multiple testing corrections. The findings provide preliminary evidence that genetic variation in genes involved in DRD2 expression and density (ANKK1) and dopamine transport (SLC6A3) plays a role in neurobehavioral recovery following pediatric TBI.

  5. Global Proteomic Analysis of Brain Tissues in Transient Ischemia Brain Damage in Rats

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    Jiann-Hwa Chen

    2015-05-01

    Full Text Available Ischemia-reperfusion injury resulting from arterial occlusion or hypotension in patients leads to tissue hypoxia with glucose deprivation, which causes endoplasmic reticulum (ER stress and neuronal death. A proteomic approach was used to identify the differentially expressed proteins in the brain of rats following a global ischemic stroke. The mechanisms involved the action in apoptotic and ER stress pathways. Rats were treated with ischemia-reperfusion brain injuries by the bilateral occlusion of the common carotid artery. The cortical neuron proteins from the stroke animal model (SAM and the control rats were separated using two-dimensional gel electrophoresis (2-DE to purify and identify the protein profiles. Our results demonstrated that the SAM rats experienced brain cell death in the ischemic core. Fifteen proteins were expressed differentially between the SAM rats and control rats, which were assayed and validated in vivo and in vitro. Interestingly, the set of differentially expressed, down-regulated proteins included catechol O-methyltransferase (COMT and cathepsin D (CATD, which are implicated in oxidative stress, inflammatory response and apoptosis. After an ischemic stroke, one protein spot, namely the calretinin (CALB2 protein, showed increased expression. It mediated the effects of SAM administration on the apoptotic and ER stress pathways. Our results demonstrate that the ischemic injury of neuronal cells increased cell cytoxicity and apoptosis, which were accompanied by sustained activation of the IRE1-alpha/TRAF2, JNK1/2, and p38 MAPK pathways. Proteomic analysis suggested that the differential expression of CALB2 during a global ischemic stroke could be involved in the mechanisms of ER stress-induced neuronal cell apoptosis, which occurred via IRE1-alpha/TRAF2 complex formation, with activation of JNK1/2 and p38 MAPK. Based on these results, we also provide the molecular evidence supporting the ischemia

  6. Application of Various Statistical Models to Explore Gene-Gene Interactions in Folate, Xenobiotic, Toll-Like Receptor and STAT4 Pathways that Modulate Susceptibility to Systemic Lupus Erythematosus.

    Science.gov (United States)

    Rupasree, Yedluri; Naushad, Shaik Mohammad; Varshaa, Ravi; Mahalakshmi, Govindaraj Swathika; Kumaraswami, Konda; Rajasekhar, Liza; Kutala, Vijay Kumar

    2016-02-01

    In view of our previous studies showing an independent association of genetic polymorphisms in folate, xenobiotic, and toll-like receptor (TLR) pathways with the risk for systemic lupus erythematosus (SLE), we have developed three statistical models to delineate complex gene-gene interactions between folate, xenobiotic, TLR, and signal transducer and activator of transcription 4 (STAT4) signaling pathways in association with the molecular pathophysiology of SLE. We developed additive, multifactor dimensionality reduction (MDR), and artificial neural network (ANN) models. The additive model, although the simplest, suggested a moderate predictability of 30 polymorphisms of these four pathways (area under the curve [AUC] 0.66). MDR analysis revealed significant gene-gene interactions among glutathione-S-transferase (GST)T1 and STAT4 (rs3821236 and rs7574865) polymorphisms, which account for moderate predictability of SLE. The MDR model for specific auto-antibodies revealed the importance of gene-gene interactions among cytochrome P450, family1, subfamily A, polypeptide 1 (CYP1A1) m1, catechol-O-methyltransferase (COMT) H108L, solute carrier family 19 (folate transporter), member 1 (SLC19A1) G80A, estrogen receptor 1 (ESR1), TLR5, 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR), thymidylate synthase (TYMS). and STAT4 polymorphisms. The ANN model for disease prediction showed reasonably good predictability of SLE risk with 30 polymorphisms (AUC 0.76). These polymorphisms contribute towards the production of SSB and anti-dsDNA antibodies to the extent of 48 and 40%, respectively, while their contribution for the production of antiRNP, SSA, and anti-cardiolipin antibodies varies between 20 and 30%. The current study highlighted the importance of genetic polymorphisms in folate, xenobiotic, TLR, and STAT4 signaling pathways as moderate predictors of SLE risk and delineates the molecular pathophysiology associated with these single nucleotide

  7. Higher FKBP5, COMT, CHRNA5, and CRHR1 allele burdens are associated with PTSD and interact with trauma exposure: implications for neuropsychiatric research and treatment

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    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

  8. Inhibition potential of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolites on the in vitro monoamine oxidase (MAO)-catalyzed deamination of the neurotransmitters serotonin and dopamine.

    Science.gov (United States)

    Steuer, Andrea E; Boxler, Martina I; Stock, Lorena; Kraemer, Thomas

    2016-01-22

    Neurotoxicity of 3,4-methylenedioxymethamphetamine (MDMA) is still controversially discussed. Formation of reactive oxygen species e.g. based on elevated dopamine (DA) concentrations and DA quinone formation is discussed among others. Inhibition potential of MDMA metabolites regarding neurotransmitter degradation by catechol-O-methyltransferase and sulfotransferase was described previously. Their influence on monoamine oxidase (MAO) - the major DA degradation pathway-has not yet been studied in humans. Therefore the inhibition potential of MDMA and its metabolites on the deamination of the neurotransmitters DA and serotonin (5-HT) by MAO-A and B using recombinant human enzymes in vitro should be investigated. In initial studies, MDMA and MDA showed relevant inhibition (>30%) toward MAO A for 5-HT and DA. No relevant effects toward MAO B were observed. Further investigation on MAO-A revealed MDMA as a competitive inhibitor of 5-HT and DA deamination with Ki 24.5±7.1 μM and 18.6±4.3 μM respectively and MDA as a mixed-type inhibitor with Ki 7.8±2.6 μM and 8.4±3.2 μM respectively. Although prediction of in vivo relevance needs to be done with care, relevant inhibitory effects at expected plasma concentrations after recreational MDMA consumption seems unlikely based on the obtained data. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Étude archéométrique du verre du Ve au XIIe siècle en Bourgogne et Franche-Comté

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    Pactat, Inès

    2013-01-01

    National audience; Depuis une quinzaine d'années, les recherches archéologiques sur le haut Moyen Âge se sont multipliées en Bourgogne et en Franche-Comté. Nos connaissances sur cette période ne se limitent plus seulement aux données fournies par les contextes funéraires. Plus d'une trentaine de sites d'habitat sont désormais répertoriés dans les deux régions. Le maillage des établissements religieux s'est également densifié avec la mise au jour de plusieurs églises paléochrétiennes et la mis...

  10. Putative therapeutic targets for symptom subtypes of adult ADHD: D4 receptor agonism and COMT inhibition improve attention and response inhibition in a novel translational animal model.

    Science.gov (United States)

    Tomlinson, Anneka; Grayson, Ben; Marsh, Samuel; Hayward, Andrew; Marshall, Kay M; Neill, Joanna C

    2015-04-01

    Prefrontal cortical dopamine plays an important role in cognitive control, specifically in attention and response inhibition; the core deficits in ADHD. We have previously shown that methylphenidate and atomoxetine differentially improve these deficits dependent on baseline performance. The present study extends this work to investigate the effects of putative therapeutic targets in our model. A selective dopamine D4 receptor agonist (A-412997) and the catechol-O-methyl-transferase (COMT) inhibitor; tolcapone, were investigated in the combined subtype of adult ADHD (ADHD-C). Adult female rats were trained to criterion in the 5C-CPT (5-Choice Continuous Performance Task) and then separated into subgroups according to baseline levels of sustained attention, vigilance, and response disinhibition. The subgroups included: high-attentive (HA) and low-attentive with high response disinhibition (ADHD-C). The ADHD-C subgroup was selected to represent the combined subtype of adult ADHD. Effects of tolcapone (3.0, 10.0, 15.0mg/kg) and A-412997 (0.1, 0.3, 1.0µmol/kg) were tested by increasing the variable inter-trial-interval (ITI) duration in the 5C-CPT. Tolcapone (15mg/kg) significantly increased sustained attention, vigilance and response inhibition in ADHD-C animals, and impaired attention in HA animals. A-412997 (1.0µmol/kg) significantly increased vigilance and response inhibition in ADHD-C animals only, with no effect in HA animals. This is the first study to use the translational 5C-CPT to model the adult ADHD-C subtype in rats and to study new targets in this model. Both tolcapone and A-412997 increased vigilance and response inhibition in the ADHD-C subgroup. D4 and COMT are emerging as important potential therapeutic targets in adult ADHD that warrant further investigation. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  11. A specific radioenzymatic assay for dihydroxyphenylalanine (DOPA). Plasma DOPA may be the precursor of urine free dopamine

    International Nuclear Information System (INIS)

    Brown, M.J.; Dollery, C.T.

    1981-01-01

    A sensitive radioenzymatic assay was developed, in which DOPA is enzymatically decarboxylated to dopamine and the latter converted to [ 3 H]-methoxytryamine in the presence of [ 3 H]-S-adenosyl-L-methionine and catechol-o-methyltransferase. The assay was specific for DOPA, and was sensitive to 50 pg/ml. Endogenous DOPA was found to be present in the plasma of eight human volunteers at a concentration of 10.46 +- 2.42 nmol/l. Simultaneous urine collections in the same subjects showed a free dopamine excretion of 68.88 +- 17.70 nmol/h. There was a significant correlation (P < 0.01) between plasma DOPA concentration and urine free dopamine excretion (r = 0.84). After the oral administration of 250 mg levodopa, plasma DOPA and urine dopamine both increased by a similar proportion (98 +- 8.4-fold, and 93.4 +- 6.9-fold respectively). These compare with an increase in plasma dopamine of only 26 +- 15-fold (P<0.01). Following the oral dose of DOPA, the increase in plasma DOPA, but not plasma dopamine, could account for the increase in urine dopamine. The calculated clearance of plasma DOPA by renal decarboxylation to dopamine was 114 +- 20 ml/min. This is not significantly different from the apparent clearance of endogenous DOPA by renal decarboxylation to dopamine, and suggests that there is adequate renal decarboxylase activity for DOPA to be the precursor for renal dopamine formation. (author)

  12. A radioenzymatic technique for the measurement of free and conjugated 3,4-dihydroxyphenylethyleneglycol in brain tissue and biological fluids

    International Nuclear Information System (INIS)

    Dennis, T.; Scatton, B.

    1982-01-01

    A simple, sensitive and specific radioenzymatic assay for the measurement of 3,4-dihydroxyphenylethyleneglycol (DOPEG) was developed. The assay is based on the conversion of the compound to its O-methylated derivative in the presence of catechol-O-methyltransferase and [ 3 H]S-adenosyl-methionine. The tritiated 3-methoxy-4-hydroxyphenylethyleneglycol formed is selectively extracted in organic solvents and isolated by thin layer chromatography. After oxidation to vanillin the O-methylated compound is extracted and measured by liquid scintillation spectrophotometry. This assay has been applied to the measurement of free and conjugated DOPEG is a variety of biological tissues and fluids. Both free and conjugated DOPEG were readily detected in discrete rat brain areas. Substantial amounts of free and conjugated DOPEG were also measured in ventricular perfusates from freely moving rats. Finally, the presence of DOPEG was also demonstrated in human cerebrospinal fluid, plasma and urine. Only the free form of DOPEG was found in cerebrospinal fluid, whereas both unconjugated and conjugated forms were present in plasma and urine. (Auth.)

  13. Polymorphisms in genes involved in the estrogen pathway and mammographic density

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    Dumas Isabelle

    2010-11-01

    Full Text Available Abstract Background Single nucleotide polymorphisms (SNPs in genes involved in the estrogen pathway appear to be associated with breast cancer risk and possibly with mammographic density (MD, but little is known of these associations among premenopausal women. This study examines the association of 11 polymorphisms in five estrogen-related genes (estrogen receptors alpha and beta (ERα, ERβ, 17β-hydroxysteroid dehydrogenase 1 (HSD17B1, catechol-O-methyltransferase (COMT, cytochrome P450 1B1 (CYP1B1 with premenopausal MD. Effect modification of four estrogen-related factors (parity, age at menarche, hormonal derivatives use and body mass index (BMI on this relation is also assessed. Methods Polymorphisms were genotyped in 741 premenopausal Caucasian women whose MD was measured in absolute density (AD, cm2 and percent density using a computer-assisted method. Multivariate linear models were used to examine the associations (Ptrend and interactions (Pi. Results None of the SNPs showed a statistically significant association with AD. However, each additional rare allele of rs1056836 CYP1B1 was associated with a reduction in AD among nulliparous women (Ptrend = 0.004, while no association was observed among parous women (Ptrend = 0.62; Pi = 0.02. An increase in the number of rare alleles of the HSD17B1 SNP (rs598126 and rs2010750 was associated with an increase in AD among women who never used hormonal derivatives (Ptrend = 0.06 and Ptrend = 0.04, respectively, but with a decrease in AD among past hormonal derivatives users (Ptrend = 0.04; Pi = 0.02 and Ptrend = 0.08; Pi = 0.01, respectively. Moreover, a negative association of rs598126 HSD17B1 SNP with AD was observed among women with higher BMI (>median (Ptrend = 0.01; Pi = 0.02. A negative association between an increased number of rare alleles of COMT rs4680 SNP and AD was limited to women who never used hormonal derivatives (Ptrend = 0.02; Pi = 0.03 or with late age at menarche (>median

  14. Ordem e Progresso: Augusto Comte e as influências do Positivismo na educação das mulheres na Primeira República brasileira

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    Loraine Lopes de Oliveira

    2018-04-01

    Full Text Available O presente artigo tem como objetivo apresentar uma reflexão acerca da influência do Positivismo na educação das mulheres no contexto da Primeira República brasileira (1889-1930, também chamada de República Velha. Faz-se uma breve abordagem inicial a respeito de Augusto Comte e o surgimento da filosofia positivista e posteriormente se discorre sobre a influência do Positivismo na educação das mulheres, a qual era vista como um elemento chave para a concretização da nova sociedade que se projetava, para o progresso e a modernização. A pesquisa tem caráter bibliográfico e fundamenta-se nos pressupostos teóricos do materialismo histórico-dialético, que busca compreender os fenômenos sociais e históricos a partir da existência material dos homens. A discussão prioriza a relação da educação com os fatores econômicos, políticos e sociais, já que se compreende que o objeto de pesquisa não pode ser entendido como uma situação isolada de seu contexto histórico. Palavras-chave: Positivismo. Primeira República Brasileira. Educação das mulheres.   Order and Progress: Augusto Comte and the influences of Positivism in the education of women in the First Brazilian Republic ABSTRACT The present article aims to present a reflection on the influence of positivism in the education of women in the context of the First Brazilian Republic (1889-1930, also called the Old Republic. A brief initial approach is given to Augusto Comte and the emergence of the positivist philosophy and later it talks about the influence of positivism in the education of women, a qualitative perspective as a key element for a concretization of the new society which was projected, for progress and modernization. The research has a bibliographic character and is based on the theoretical assumptions of historical-dialectical materialism, which seeks social and historical phenomena from the material reality of men. The discussion prioritizes the relationship

  15. Comentario sobre el libro de Enric Saguer Hom, Gabriel Jover Avellà y Helena Benito Mundet (eds.: Comtes de senyor, comtes de pagès. Les comptabilitats agràries en la historia rural. Associació d'Història Rural de les Comarques Gironines. Centre de Recerca Històrica Rural (Institut de Recerca Històrica de la Universitat de Girona i Documenta Universitaria (Biblioteca d'Història Rural, col·lecció Fonts, 7, Girona, 2013

    Directory of Open Access Journals (Sweden)

    Gaspar Feliu

    2014-07-01

    Full Text Available Comentario sobre el libro de Enric Saguer Hom, Gabriel Jover Avellà y Helena Benito Mundet (eds.: Comtes de senyor, comtes de pagès. Les comptabilitats agràries en la historia rural. Associació d'Història Rural de les Comarques Gironines. Centre de Recerca Històrica Rural (Institut de Recerca Històrica de la Universitat de Girona i Documenta Universitaria (Biblioteca d'Història Rural, col·lecció Fonts, 7, Girona, 2013

  16. [Evaluation of the management of soft tissue sarcomas in Franche-Comté since the establishment of a multidisciplinary meeting at University Hospital. About 47 cases].

    Science.gov (United States)

    Haddad, J; Kalbacher, E; Piccard, M; Aubry, S; Chaigneau, L; Pauchot, J

    2017-02-01

    A multidisciplinary meeting (RCP) dedicated to the treatment of sarcoma was established in Franche-Comte in 2010. The goals of the study are: (a) To evaluate the treatment of sarcomas by confrontation with the existing literature; (b) To evaluate the influence of the multidisciplinary meeting on the management of sarcomas by hospitals at the regional level. This is a retrospective single center study from 2010 to 2015 on patients with sarcoma and peripheral soft tissue drawn from a Netsarc database (National Network of sarcomas) and communicating cancer record. A database Cleanweb especially dedicated is created. Forty-seven patients were included: ten sarcomas at the upper member 26 to the lower limbs, 11 on the trunk. Forty patients were operated on: ten out of the university hospital, 28 at the university hospital and two in a coordinating center. Ninety percent of patients treated at the university hospital were in accordance with the recommandations. None of the patients operated out of the university hospital benefited from medical care in accordance to the recommendations. There is an increase in the number of files sent by the hospitals out of the university hospital discussed in multidisciplinary meeting, before treatment. The creation of a dedicated multidisciplinary meeting sarcoma improves the medical management of these tumors and decreases inappropriate medical managements thanks to a better education of the regional physicians. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  17. Llenguatge jurídic i llenguatge poètic: les gosadies del comte-bisbe Miró Bonfill

    Directory of Open Access Journals (Sweden)

    Quetglas, Pere J.

    2015-06-01

    Full Text Available This paper addresses the poetic originality of Miró Bonfill, count of Besalú and bishop of Girona (tenth century, in one of the documents attributed to him: the provision certificate of the church of Sant Pere de Besalú. The analysis of the 27 verses contained in this document shows an evident dependence on poets like Paulinus of Aquileia and Venantius Fortunatus, but it also allows to trace connections with other contemporary and later works. This fact poses new questions on the literary links between Catalonia and Europe in the tenth century.[ct] En aquest treball s’estudia l’originalitat poètica del comte de Besalú i Bisbe de Girona, Miró Bonfill (segle X, en un dels documents que hom li atribueix: l’acta de confirmació de la dotació de l’església de Sant Pere de Besalú. L’anàlisi dels 27 versos identificats en aquest document posen en relleu una clara dependència de Miró Bonfill d’altres poetes com Paulí d’Aquileia o Venanci Fortunat, però també l’existència de relacions amb altres obres, anteriors, contemporànies i posteriors, circumstància que obre nous interrogants sobre les relacions literàries de Catalunya amb Europa al segle X.

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

    Science.gov (United States)

    González-Giraldo, Yeimy; Camargo, Andrés; López-León, Sandra; Forero, Diego A

    2015-01-01

    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.

  19. Therapeutic interventions and adjustments in the management of Parkinson disease: role of combined carbidopa/levodopa/entacapone (Stalevo®

    Directory of Open Access Journals (Sweden)

    Paolo Solla

    2010-08-01

    Full Text Available Paolo Solla, Antonino Cannas, Francesco Marrosu, Maria Giovanna MarrosuMovement Disorders Center, Institute of Neurology, University of Cagliari, Cagliari, ItalyAbstract: Parkinson disease (PD is a neurodegenerative disorder characterized by 3 cardinal motor symptoms: resting tremor, rigidity, and bradykinesia. Since its introduction 40 years ago, levodopa has represented the gold standard for dopaminergic stimulation therapy in patients with PD. Levodopa is routinely combined with a dopa-decarboxylase inhibitor (DDCI to prevent the conversion of levodopa into dopamine in peripheral circulation. However, up to 80% of patients treated with continuous levodopa manifest the onset of disabling motor complications capable of producing an adverse effect on quality of life as the disease progresses. In recent years, a new, safe, and efficacious armamentarium of treatment options has been provided by the marketing of the catechol-O-methyltransferase (COMT inhibitor, entacapone, a peripheral blocker of dopa to 3-0-methyldopa metabolism, which increments levodopa brain availability. When administered with levodopa, entacapone conjugates the rapid onset of levodopa-induced effects with a protracted efficiency, thus providing additional benefits to classic levodopa treatment by increasing “on” time in fluctuating PD patients, and theoretically providing a more continuous and physiological-like stimulation of dopamine receptors implying a reduced risk of motor complications. In this context, the use of a single administration of combined ­carbidopa/levodopa/entacapone (Stalevo® in the treatment of PD affords clinical improvements similar to those obtained by 2 separate tablets (ie, levodopa/DDCI and entacapone, although the former produces a more positive effect on quality of life than the latter. Additionally, the STalevo Reduction In Dyskinesia Evaluation (STRIDE-PD study was designed with the aim of demonstrating that the combination of levodopa

  20. Dietary quercetin exacerbates the development of estrogen-induced breast tumors in female ACI rats

    International Nuclear Information System (INIS)

    Singh, Bhupendra; Mense, Sarah M.; Bhat, Nimee K.; Putty, Sandeep; Guthiel, William A.; Remotti, Fabrizio; Bhat, Hari K.

    2010-01-01

    Phytoestrogens are plant compounds that structurally mimic the endogenous estrogen 17β-estradiol (E 2 ). Despite intense investigation, the net effect of phytoestrogen exposure on the breast remains unclear. The objective of the current study was to examine the effects of quercetin on E 2 -induced breast cancer in vivo. Female ACI rats were given quercetin (2.5 g/kg food) for 8 months. Animals were monitored weekly for palpable tumors, and at the end of the experiment, rats were euthanized, breast tumor and different tissues excised so that they could be examined for histopathologic changes, estrogen metabolic activity and oxidant stress. Quercetin alone did not induce mammary tumors in female ACI rats. However, in rats implanted with E 2 pellets, co-exposure to quercetin did not protect rats from E 2 -induced breast tumor development with 100% of the animals developing breast tumors within 8 months of treatment. No changes in serum quercetin levels were observed in quercetin and quercetin + E 2 -treated groups at the end of the experiment. Tumor latency was significantly decreased among rats from the quercetin + E 2 group relative to those in the E 2 group. Catechol-O-methyltransferase (COMT) activity was significantly downregulated in quercetin-exposed mammary tissue. Analysis of 8-isoprostane F 2α (8-iso-PGF 2α ) levels as a marker of oxidant stress showed that quercetin did not decrease E 2 -induced oxidant stress. These results indicate that quercetin (2.5 g/kg food) does not confer protection against breast cancer, does not inhibit E 2 -induced oxidant stress and may exacerbate breast carcinogenesis in E 2 -treated ACI rats. Inhibition of COMT activity by quercetin may expose breast cells chronically to E 2 and catechol estrogens. This would permit longer exposure times to the carcinogenic metabolites of E 2 and chronic exposure to oxidant stress as a result of metabolic redox cycling to estrogen metabolites, and thus quercetin may exacerbate E 2 -induced

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

    NARCIS (Netherlands)

    Spronk, D.B.; Schaaf, M.E. van der; Cools, R.; Bruijn, E.R. De; Franke, B.; Wel, J.H. van; Ramaekers, J.G.; Verkes, R.J.

    2016-01-01

    RATIONALE: 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. OBJECTIVE: In this study, we aimed to establish the acute effects of administration of

  2. The role of clinical variables, neuropsychological performance and SLC6A4 and COMT gene polymorphisms on the prediction of early response to fluoxetine in major depressive disorder.

    Science.gov (United States)

    Gudayol-Ferré, Esteve; Herrera-Guzmán, Ixchel; Camarena, Beatriz; Cortés-Penagos, Carlos; Herrera-Abarca, Jorge E; Martínez-Medina, Patricia; Cruz, David; Hernández, Sandra; Genis, Alma; Carrillo-Guerrero, Mariana Y; Avilés Reyes, Rubén; Guàrdia-Olmos, Joan

    2010-12-01

    Major depressive disorder (MDD) is treated with antidepressants, but only between 50% and 70% of the patients respond to the initial treatment. Several authors suggested different factors that could predict antidepressant response, including clinical, psychophysiological, neuropsychological, neuroimaging, and genetic variables. However, these different predictors present poor prognostic sensitivity and specificity by themselves. The aim of our work is to study the possible role of clinical variables, neuropsychological performance, and the 5HTTLPR, rs25531, and val108/58Met COMT polymorphisms in the prediction of the response to fluoxetine after 4weeks of treatment in a sample of patient with MDD. 64 patients with MDD were genotyped according to the above-mentioned polymorphisms, and were clinically and neuropsychologically assessed before a 4-week fluoxetine treatment. Fluoxetine response was assessed by using the Hamilton Depression Rating Scale. We carried out a binary logistic regression model for the potential predictive variables. Out of the clinical variables studied, only the number of anxiety disorders comorbid with MDD have predicted a poor response to the treatment. A combination of a good performance in variables of attention and low performance in planning could predict a good response to fluoxetine in patients with MDD. None of the genetic variables studied had predictive value in our model. The possible placebo effect has not been controlled. Our study is focused on response prediction but not in remission prediction. Our work suggests that the combination of the number of comorbid anxiety disorders, an attentional variable, and two planning variables makes it possible to correctly classify 82% of the depressed patients who responded to the treatment with fluoxetine, and 74% of the patients who did not respond to that treatment. Copyright © 2010 Elsevier B.V. All rights reserved.

  3. Assessment of Climate Air Energy Regional Schemes in Burgundy and in Franche-Comte - Intermediate review on June 27, 2017. Burgundy Climate Air Energy Regional Scheme. Project, Scheme, Appendix to the SRCAE - Wind regional scheme of Burgundy, synthesis, opinion of the Burgundy CESER. Territorial Climate Energy Plan - Program of actions, Plenary session of the November 25, 2013. Climate Air Energy Regional Scheme - Franche-Comte SRCAE

    International Nuclear Information System (INIS)

    2011-09-01

    A first report proposes an assessment of the various aspects addressed by the Climate Air Energy Regional Schemes (SRCAE) of Burgundy and Franche-Comte: global aspects, and aspects related to adaptation to climate change, to air quality, to land planning, to the building sector, to mobility, to good transports, to agriculture, to forest, to industry and craft, to renewable energies, and to ecological responsibility. A synthetic presentation of the Burgundy scheme is proposed, and then an extended version which contains a description of the situation, an analysis of the regional potential, and a definition of orientations for the same above-mentioned aspects. A document more particularly addresses wind energy: role of wind energy in the energy mix of the region, role of small installations, wind energy potential, challenges and constraints (heritage and landscapes, natural environment, technical constraints), identification of areas of interest for wind energy projects, qualitative objectives. Documents published by the regional economic, social and environmental Council (CESER) of Burgundy are then proposed: a contribution to the Climate Air Energy Regional Scheme, a discussion and a presentation of a program of actions for the Climate Energy Territorial Plan (a large number of sheets of presentation of actions is proposed). The last document presents the Franche-Comte regional scheme: overview of regional knowledge on climate, air quality and environmental issues, challenges and potential per activity sector (transports and development, building, agriculture, industry, renewable energy production), definition of orientations and objectives for axes of action

  4. Proteomic analysis on the alteration of protein expression in the early-stage placental villous tissue of electromagnetic fields associated with cell phone exposure.

    Science.gov (United States)

    Luo, Qiong; Jiang, Ying; Jin, Min; Xu, Jian; Huang, He-Feng

    2013-09-01

    To explore the possible adverse effects and search for cell phone electromagnetic field (EMF)-responsive proteins in human early reproduction, a proteomics approach was employed to investigate the changes in protein expression profile induced by cell phone EMF in human chorionic tissues of early pregnancy in vivo. Volunteer women about 50 days pregnant were exposed to EMF at the average absorption rate of 1.6 to 8.8 W/kg for 1 hour with the irradiation device placed 10 cm away from the umbilicus at the midline of the abdomen. The changes in protein profile were examined using 2-dimensional electrophoresis (2-DE). Up to 15 spots have yielded significant change at least 2- to 2.5-folds up or down compared to sham-exposed group. Twelve proteins were identified- procollagen-proline, eukaryotic translation elongation factor 1 delta, chain D crystal structure of human vitamin D-binding protein, thioredoxin-like 3, capping protein, isocitrate dehydrogenase 3 alpha, calumenin, Catechol-O-methyltransferase protein, proteinase inhibitor 6 (PI-6; SerpinB6) protein, 3,2-trans-enoyl-CoA isomerase protein, chain B human erythrocyte 2,3-bisphosphoglycerate mutase, and nucleoprotein. Cell phone EMF might alter the protein profile of chorionic tissue of early pregnancy, during the most sensitive stage of the embryos. The exposure to EMF may cause adverse effects on cell proliferation and development of nervous system in early embryos. Furthermore, 2-DE coupled with mass spectrometry is a promising approach to elucidate the effects and search for new biomarkers for environmental toxic effects.

  5. 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

  6. Estrogen receptor α and aryl hydrocarbon receptor cross-talk in a transfected hepatoma cell line (HepG2 exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin

    Directory of Open Access Journals (Sweden)

    Manuela Göttel

    2014-01-01

    Full Text Available The prototype dioxin congener 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD is known to exert anti-estrogenic effects via activation of the aryl hydrocarbon receptor (AhR by interfering with the regulation of oestrogen homeostasis and the estrogen receptor α (ERα signalling pathway. The AhR/ER cross-talk is considered to play a crucial role in TCDD- and E2-dependent mechanisms of carcinogenesis, though the concerted mechanism of action in the liver is not yet elucidated. The present study investigated TCDD's impact on the transcriptional cross-talk between AhR and ERα and its modulation by 17β-estradiol (E2 in the human hepatoma cell line HepG2, which is AhR-responsive but ERα-negative. Transient transfection assays with co-transfection of hERα and supplementation of receptor antagonists showed anti-estrogenic action of TCDD via down-regulation of E2-induced ERα signaling. In contrast, enhancement of AhR signaling dependent on ERα was observed providing evidence for increased cytochrome P450 (CYP induction to promote E2 metabolism. However, relative mRNA levels of major E2-metabolizing CYP1A1 and 1B1 and the main E2-detoxifying catechol-O-methyltransferase were not affected by the co-treatments. This study provides new evidence of a TCDD-activated AhR-mediated molecular AhR/ERα cross-talk mechanism at transcriptional level via indirect inhibition of ERα and enhanced transcriptional activity of AhR in HepG2 cells.

  7. Pharmacogenetics and Pharmacotherapy of Military Personnel Suffering from Post-traumatic Stress Disorder.

    Science.gov (United States)

    Naß, Janine; Efferth, Thomas

    2017-01-01

    Posttraumatic stress disorder (PTSD) is a severe problem among soldiers with combating experience difficult to treat. The pathogenesis is still not fully understood at the psychological level. Therefore, genetic research became a focus of interest. The identification of single nucleotide polymorphisms (SNPs) may help to predict, which persons are at high risk to develop PTSD as a starting point to develop novel targeted drugs for treatment. We conducted a systematic review on SNPs in genes related to PTSD pathology and development of targeted pharmacological treatment options based on PubMed database searches. We focused on clinical trials with military personnel. SNPs in 22 human genes have been linked to PTSD. These genes encode proteins acting as neurotransmitters and receptors, downstream signal transducers and metabolizing enzymes. Pharmacological inhibitors may serve as drug candidates for PTSD treatment, e.g. β2 adrenoreceptor antagonists, dopamine antagonists, partial dopamine D2 receptor agonists, dopamine β hydroxylase inhibitors, fatty acid amid hydrolase antagonists, glucocorticoid receptor agonists, tropomyosin receptor kinase B agonists, selective serotonin reuptake inhibitors, catechol-O-methyltransferase inhibitors, gamma-amino butyric acid receptor agonists, glutamate receptor inhibitors, monoaminoxidase B inhibitors, N-methyl-d-aspartate receptor antagonists. The combination of genetic and pharmacological research may lead to novel targetbased drug developments with improved specificity and efficacy to treat PTSD. Specific SNPs may be identified as reliable biomarkers to assess individual disease risk. Focusing on soldiers suffering from PTSD will not only help to improve treatment options for this specific group, but for all PTSD patients and the general population. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Medical management of levodopa-associated motor complications in patients with Parkinson's disease.

    Science.gov (United States)

    Jankovic, Joseph; Stacy, Mark

    2007-01-01

    Parkinson's disease is a neurodegenerative disorder that affects approximately 1% of people over the age of 60 years. Levodopa is standard, and often initial, therapy for patients with this condition; however, with continued treatment and as the disease progresses, up to 80% of patients experience 'wearing-off' symptoms, dyskinesias and other motor complications. These levodopa-associated problems may become disabling and profoundly affect quality of life. Medications commonly used to manage these symptoms include monoamine oxidase type B (MAO-B) inhibitors, catechol-O-methyltransferase (COMT) inhibitors, the NMDA receptor antagonist amantadine and dopamine receptor agonists. Agents that block MAO-B, such as rasagiline and selegiline, are used as both initial and adjunctive therapy in patients with Parkinson's disease. These medications increase concentrations of dopamine in the brain by blocking its reuptake from the synaptic cleft, a mechanism that can slow motor decline, increase 'on' time and improve symptoms of Parkinson's disease. Adverse events with these agents can include confusion, hallucination and orthostatic hypotension. MAO-B inhibition may elicit drug-drug interactions if administered with TCAs, SSRIs or SNRIs. Conventional oral selegiline is associated with potentially harmful plasma concentrations of three major amphetamine metabolites, although metabolite concentrations are significantly lower with a new orally disintegrating tablet (ODT) selegiline formulation. Selegiline ODT is also absorbed more efficiently and shows less pharmacokinetic variability than conventional oral selegiline.COMT mediates peripheral catabolism of levodopa. Therefore, agents that block COMT, such as tolcapone and entacapone, increase the elimination half-life of levodopa. Given adjunctively with levodopa, COMT inhibitors can decrease 'off' time and increase 'on' time, as well as lower the daily levodopa dose. Although more potent than entacapone, tolcapone requires

  9. Structure and possible mechanism of the CcbJ methyltransferase from Streptomyces caelestis

    Czech Academy of Sciences Publication Activity Database

    Bauer, J.; Ondrovičová, G.; Najmanová, Lucie; Pevala, V.; Kameník, Zdeněk; Koštan, J.; Janata, Jiří; Kutejová, Eva

    2014-01-01

    Roč. 70, APR 2014 (2014), s. 943-957 ISSN 0907-4449 R&D Projects: GA MŠk(CZ) EE2.3.30.0003; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:61388971 Keywords : CATECHOL-O-METHYLTRANSFERASE * SN2-LIKE TRANSITION-STATE * CRYSTAL-STRUCTURES Subject RIV: CE - Biochemistry Impact factor: 7.232, year: 2013

  10. Determination of plasma adrenaline and noradrenaline levels with the Cat-a-Kit

    International Nuclear Information System (INIS)

    Nel, P.B.; Du Preez, S.E.

    1980-01-01

    A method for the determination of catecholamines (Cat-a-Kit; Upjohn Diagnostics) is discussed. It depends upon the enzymatic conversion of the catecholamines to their ring o-methylated analogues in the presence of s-adenosyl-L-methionine-methyl- 14 C and catechol-o-methyltransferase. Values obtained from the blood plasma of 16 tetraplegic and 11 healthy volunteers are reported. The advantages and disadvantages of the Cat-a-Kit are discussed

  11. Polymorphisms in genes involved in the estrogen pathway and mammographic density

    International Nuclear Information System (INIS)

    Dumas, Isabelle; Diorio, Caroline

    2010-01-01

    Single nucleotide polymorphisms (SNPs) in genes involved in the estrogen pathway appear to be associated with breast cancer risk and possibly with mammographic density (MD), but little is known of these associations among premenopausal women. This study examines the association of 11 polymorphisms in five estrogen-related genes (estrogen receptors alpha and beta (ERα, ERβ), 17β-hydroxysteroid dehydrogenase 1 (HSD17B1), catechol-O-methyltransferase (COMT), cytochrome P450 1B1 (CYP1B1)) with premenopausal MD. Effect modification of four estrogen-related factors (parity, age at menarche, hormonal derivatives use and body mass index (BMI)) on this relation is also assessed. Polymorphisms were genotyped in 741 premenopausal Caucasian women whose MD was measured in absolute density (AD, cm 2 ) and percent density using a computer-assisted method. Multivariate linear models were used to examine the associations (P trend ) and interactions (P i ). None of the SNPs showed a statistically significant association with AD. However, each additional rare allele of rs1056836 CYP1B1 was associated with a reduction in AD among nulliparous women (P trend = 0.004), while no association was observed among parous women (P trend = 0.62; P i = 0.02). An increase in the number of rare alleles of the HSD17B1 SNP (rs598126 and rs2010750) was associated with an increase in AD among women who never used hormonal derivatives (P trend = 0.06 and P trend = 0.04, respectively), but with a decrease in AD among past hormonal derivatives users (P trend = 0.04; P i = 0.02 and P trend = 0.08; P i = 0.01, respectively). Moreover, a negative association of rs598126 HSD17B1 SNP with AD was observed among women with higher BMI (>median) (P trend = 0.01; P i = 0.02). A negative association between an increased number of rare alleles of COMT rs4680 SNP and AD was limited to women who never used hormonal derivatives (P trend = 0.02; P i = 0.03) or with late age at menarche (>median) (P trend = 0.03; P i

  12. Pharmacodynamic genetic polymorphisms affect adverse drug reactions of haloperidol in patients with alcohol-use disorder

    Directory of Open Access Journals (Sweden)

    Zastrozhin MS

    2017-07-01

    Full Text Available Mikhail Sergeevich Zastrozhin,1,2 Vadim Markovich Brodyansky,3 Valentin Yurievich Skryabin,4 Elena Anatolievna Grishina,5 Dmitry Vladimirovich Ivashchenko,5 Kristina Anatolievna Ryzhikova,5 Ludmila Mikhaylovna Savchenko,1 Alexander Olegovich Kibitov,3 Evgeny Alekseevich Bryun,1,4 Dmitry Alekseevich Sychev6 1Department of Addictology, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russia; 2Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Center for the Prevention of Dependent Behavior, Moscow, Russia; 3Federal Medical Research Centre of Psychiatry and Addictology, Laboratory of Molecular Genetics, Moscow, Russia; 4Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Department of Addictology, Moscow, Russia; 5Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Research Centre, Moscow, Russia; 6Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Department of Clinical Pharmacology and Therapy, Moscow, Russia Background: Antipsychotic action of haloperidol is due to blockade of D2 receptors in the mesolimbic dopamine pathway, while the adverse drug reactions are associated with striatal D2 receptor blockade. Contradictory data concerning the effects of genetic polymorphisms of genes encoding these receptors and associated structures (catechol-O-methyltransferase [COMT], glycine transporter and gene encoding the density of D2 receptors on the neuronal membrane are described.Objective: The objectives of this study were to evaluate the correlation between DRD2, SLC6A3 (DAT and COMT genetic polymorphisms and to investigate their effect on the development of adverse drug reactions in patients with alcohol-use disorder who received haloperidol.Patients and methods: The study

  13. Mind, medicine, and metaphysics: reflections on the reclamation of the human spirit.

    Science.gov (United States)

    Penn, Michael L; Wilson, Lindsay

    2003-01-01

    Following the publication of such works as Auguste Comte's Cour de Philosophie Positive (1830-1842), in which he argued the inherent immaturity of metaphysical discourse, metaphysics, for Western intellectuals--and especially for Western intellectuals committed to science--has largely been abandoned. In recent years, however, we have seen renewed interest in metaphysics among some researchers and clinicians, due, in part, to increasing attempts to integrate diverse fields of study into some unified and coherent understanding of human life. For many psychologists and psychiatrists, this renewed interest is accompanied by an implicit, and sometimes explicit, re-embrace of the notion of the "human spirit." In this paper we explore some of the processes animating this movement and some of the clinical implications that flow from it.

  14. Impact of newer pharmacological treatments on quality of life in patients with Parkinson's disease.

    Science.gov (United States)

    Gallagher, David A; Schrag, Anette

    2008-01-01

    Parkinson's disease is a common progressive neurodegenerative condition with multiple motor and nonmotor features contributing to impairment of health-related quality of life (HR-QOL). Pharmacological treatments have been directed primarily at dopamine replacement with levodopa and agents to improve its bioavailability, including DOPA decarboxylase inhibitors, catechol-O-methyltransferase (COMT) inhibitors and monoamine oxidase B (MAO-B) inhibitors, as well as synthetic dopamine agonists. These treatments to restore motor function are often very successful in early Parkinson's disease, with objective improvement and concomitant improvement in subjective HR-QOL scores. However, as the disease progresses, motor complications and nonmotor symptoms predominate and are often refractory to therapeutic interventions. Antiparkinsonian medications have been shown to improve motor severity and motor complications of advancing disease, and there is increasing evidence that this can be translated into subjective improvement of HR-QOL from a patient's point of view. However, the degree of improvement is less marked on HR-QOL scores than on motor scores, and some studies do not show improvement of HR-QOL in parallel to motor improvements. A number of explanations are possible, including limitations of the scales used, trial designs and lack of clinical improvement from the patients' point of view. This review concentrates on clinical trials with an index of HR-QOL as an outcome measure, with particular emphasis on well designed, randomized, double-blind, placebo-controlled or active comparator-controlled methodology. Drugs that have been more recently added to the armamentarium of Parkinson's disease, including the oral (pramipexole, ropinirole and piribedil) and transdermal (rotigotine) non-ergotamine-derived dopamine agonists, the novel MAO-B inhibitor rasagiline and the COMT inhibitors tolcapone and entacapone, were included. The effect of each of these agents on overall HR

  15. Comparison of molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) and molecular mechanics-three-dimensional reference interaction site model (MM-3D-RISM) method to calculate the binding free energy of protein-ligand complexes: Effect of metal ion and advance statistical test

    Science.gov (United States)

    Pandey, Preeti; Srivastava, Rakesh; Bandyopadhyay, Pradipta

    2018-03-01

    The relative performance of MM-PBSA and MM-3D-RISM methods to estimate the binding free energy of protein-ligand complexes is investigated by applying these to three proteins (Dihydrofolate Reductase, Catechol-O-methyltransferase, and Stromelysin-1) differing in the number of metal ions they contain. None of the computational methods could distinguish all the ligands based on their calculated binding free energies (as compared to experimental values). The difference between the two comes from both polar and non-polar part of solvation. For charged ligand case, MM-PBSA and MM-3D-RISM give a qualitatively different result for the polar part of solvation.

  16. More Human than Human.

    Science.gov (United States)

    Lawrence, David

    2017-07-01

    Within the literature surrounding nonhuman animals on the one hand and cognitively disabled humans on the other, there is much discussion of where beings that do not satisfy the criteria for personhood fit in our moral deliberations. In the future, we may face a different but related problem: that we might create (or cause the creation of) beings that not only satisfy but exceed these criteria. The question becomes whether these are minimal criteria, or hierarchical, such that those who fulfill them to greater degree should be afforded greater consideration. This article questions the validity and necessity of drawing divisions among beings that satisfy the minimum requirements for personhood; considering how future beings-intelligent androids, synthezoids, even alternate-substrate sentiences-might fit alongside the "baseline" human. I ask whether these alternate beings ought to be considered different to us, and why this may or may not matter in terms of a notion of "human community." The film Blade Runner, concerned in large part with humanity and its key synthezoid antagonist Roy Batty, forms a framing touchstone for my discussion. Batty is stronger, faster, more resilient, and more intelligent than Homo sapiens. His exploits, far beyond the capability of normal humans, are contrasted with his frailty and transient lifespan, his aesthetic appreciation of the sights he has seen, and his burgeoning empathy. Not for nothing does his creator within the mythos term him "more human than human."

  17. Human engineering

    International Nuclear Information System (INIS)

    Yang, Seong Hwan; Park, Bum; Gang, Yeong Sik; Gal, Won Mo; Baek, Seung Ryeol; Choe, Jeong Hwa; Kim, Dae Sung

    2006-07-01

    This book mentions human engineering, which deals with introduction of human engineering, Man-Machine system like system design, and analysis and evaluation of Man-Machine system, data processing and data input, display, system control of man, human mistake and reliability, human measurement and design of working place, human working, hand tool and manual material handling, condition of working circumstance, working management, working analysis, motion analysis working measurement, and working improvement and design in human engineering.

  18. Human rights

    NARCIS (Netherlands)

    Gaay Fortman, B. de

    2006-01-01

    Human rights reflect a determined effort to protect the dignity of each and every human being against abuse of power. This endeavour is as old as human history. What is relatively new is the international venture for the protection of human dignity through internationally accepted legal standards

  19. Human reliability

    International Nuclear Information System (INIS)

    Embrey, D.E.

    1987-01-01

    Concepts and techniques of human reliability have been developed and are used mostly in probabilistic risk assessment. For this, the major application of human reliability assessment has been to identify the human errors which have a significant effect on the overall safety of the system and to quantify the probability of their occurrence. Some of the major issues within human reliability studies are reviewed and it is shown how these are applied to the assessment of human failures in systems. This is done under the following headings; models of human performance used in human reliability assessment, the nature of human error, classification of errors in man-machine systems, practical aspects, human reliability modelling in complex situations, quantification and examination of human reliability, judgement based approaches, holistic techniques and decision analytic approaches. (UK)

  20. Human Rights, Human Needs, Human Development, Human Security

    OpenAIRE

    Gasper, Des

    2009-01-01

    Human rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and politics; each has emerged within the United Nations world; each relies implicitly on a conceptualisation of human need; each has specific strengths. Yet mutual communication, understanding and co-operation are deficient, espec...

  1. Human niche, human behaviour, human nature.

    Science.gov (United States)

    Fuentes, Agustin

    2017-10-06

    The concept of a 'human nature' or 'human natures' retains a central role in theorizing about the human experience. In Homo sapiens it is clear that we have a suite of capacities generated via our evolutionary past, and present, and a flexible capacity to create and sustain particular kinds of cultures and to be shaped by them. Regardless of whether we label these capacities 'human natures' or not, humans occupy a distinctive niche and an evolutionary approach to examining it is critical. At present we are faced with a few different narratives as to exactly what such an evolutionary approach entails. There is a need for a robust and dynamic theoretical toolkit in order to develop a richer, and more nuanced, understanding of the cognitively sophisticated genus Homo and the diverse sorts of niches humans constructed and occupied across the Pleistocene, Holocene, and into the Anthropocene. Here I review current evolutionary approaches to 'human nature', arguing that we benefit from re-framing our investigations via the concept of the human niche and in the context of the extended evolutionary synthesis (EES). While not a replacement of standard evolutionary approaches, this is an expansion and enhancement of our toolkit. I offer brief examples from human evolution in support of these assertions.

  2. Renewable energies in Franche-Comte 2008 - 2010 - 2012 - 2014

    International Nuclear Information System (INIS)

    2015-12-01

    Illustrated by maps and tables, this publication proposes an overview of the evolution of installed power and production of renewable electric power (by hydroelectric, solar photovoltaic, and wind energy), of renewable electricity and heat (by wood-energy, biogas, and recovery energy), of renewable heat (by solar thermal energy, very low energy geothermal energy and heat pumps, and wood-energy). It also briefly indicates the situation of biogas, agri-fuel and bio-fuel production

  3. Human Smuggling

    NARCIS (Netherlands)

    Siegel - Rozenblit, Dina; Zaitch, Damian

    2014-01-01

    Human smuggling is based on a consensus between smuggler, smuggled, and his/her family (which usually guarantees or effectuates payment). However, unauthorized immigrants are violating immigration laws and human smugglers are profiting from enabling illegal immigration. Both human smuggling and its

  4. Human intrusion

    International Nuclear Information System (INIS)

    Hora, S.; Neill, R.; Williams, R.; Bauser, M.; Channell, J.

    1993-01-01

    This paper focused on the possible approaches to evaluating the impacts of human intrusion on nuclear waste disposal. Several major issues were reviewed. First, it was noted that human intrusion could be addressed either quantitatively through performance assessments or qualitatively through design requirements. Second, it was decided that it was impossible to construct a complete set of possible future human intrusion scenarios. Third, the question of when the effect of possible human intrusion should be considered, before or after site selection was reviewed. Finally, the time frame over which human intrusion should be considered was discussed

  5. Human Technology and Human Affects

    DEFF Research Database (Denmark)

    Fausing, Bent

    2009-01-01

    Human Technology and Human Affects  This year Samsung introduced a mobile phone with "Soul". It was made with a human touch and included itself a magical touch. Which function does technology and affects get in everyday aesthetics like this, its images and interactions included this presentation...... will ask and try to answer. The mobile phone and its devices are depicted as being able to make a unique human presence, interaction, and affect. The medium, the technology is a necessary helper to get towards this very special and lost humanity. Without the technology, no special humanity - soul....... The paper will investigate how technology, humanity, affects, and synaesthesia are presented and combined with examples from everyday aesthetics, e.g. early computer tv-commercial, net-commercial for mobile phones. Technology and affects point, is the conclusion, towards a forgotten pre-human and not he...

  6. Human Parvoviruses

    Science.gov (United States)

    Söderlund-Venermo, Maria; Young, Neal S.

    2016-01-01

    SUMMARY Parvovirus B19 (B19V) and human bocavirus 1 (HBoV1), members of the large Parvoviridae family, are human pathogens responsible for a variety of diseases. For B19V in particular, host features determine disease manifestations. These viruses are prevalent worldwide and are culturable in vitro, and serological and molecular assays are available but require careful interpretation of results. Additional human parvoviruses, including HBoV2 to -4, human parvovirus 4 (PARV4), and human bufavirus (BuV) are also reviewed. The full spectrum of parvovirus disease in humans has yet to be established. Candidate recombinant B19V vaccines have been developed but may not be commercially feasible. We review relevant features of the molecular and cellular biology of these viruses, and the human immune response that they elicit, which have allowed a deep understanding of pathophysiology. PMID:27806994

  7. Human Rights/Human Needs.

    Science.gov (United States)

    Canning, Cynthia

    1978-01-01

    The faculty of Holy Names High School developed an interdisciplinary human rights program with school-wide activities focusing on three selected themes: the United Nations Universal Declaration of Human Rights, in conjunction with Human Rights Week; Food; and Women. This article outlines major program activities. (SJL)

  8. From observational to analytical morphology of the stratum corneum: progress avoiding hazardous animal and human testings

    Directory of Open Access Journals (Sweden)

    Piérard GE

    2015-03-01

    Full Text Available Gérald E Piérard,1,2 Justine Courtois,1 Caroline Ritacco,1 Philippe Humbert,2,3 Ferial Fanian,3 Claudine Piérard-Franchimont1,4,5 1Laboratory of Skin Bioengineering and Imaging (LABIC, Department of Clinical Sciences, Liège University, Liège, Belgium; 2University of Franche-Comté, Besançon, France; 3Department of Dermatology, University Hospital Saint-Jacques, Besançon, France; 4Department of Dermatopathology, Unilab Lg, University Hospital of Liège, Liège, Belgium; 5Department of Dermatology, Regional Hospital of Huy, Huy, Belgium Background: In cosmetic science, noninvasive sampling of the upper part of the stratum corneum is conveniently performed using strippings with adhesive-coated discs (SACD and cyanoacrylate skin surface strippings (CSSSs. Methods: Under controlled conditions, it is possible to scrutinize SACD and CSSS with objectivity using appropriate methods of analytical morphology. These procedures apply to a series of clinical conditions including xerosis grading, comedometry, corneodynamics, corneomelametry, corneosurfametry, corneoxenometry, and dandruff assessment. Results: With any of the analytical evaluations, SACD and CSSS provide specific salient information that is useful in the field of cosmetology. In particular, both methods appear valuable and complementary in assessing the human skin compatibility of personal skincare products. Conclusion: A set of quantitative analytical methods applicable to the minimally invasive and low-cost SACD and CSSS procedures allow for a sound assessment of cosmetic effects on the stratum corneum. Under regular conditions, both methods are painless and do not induce adverse events. Globally, CSSS appears more precise and informative than the regular SACD stripping. Keywords: irritation, morphometry, quantitative morphology, stripping

  9. Human Rights, Human Needs, Human Development, Human Security - Relationships between four international human discourses.

    NARCIS (Netherlands)

    D.R. Gasper (Des)

    2007-01-01

    markdownabstractAbstract: Human rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and

  10. Human evolution

    DEFF Research Database (Denmark)

    Llamas, Bastien; Willerslev, Eske; Orlando, Ludovic Antoine Alexandre

    2017-01-01

    The field of human ancient DNA (aDNA) has moved from mitochondrial sequencing that suffered from contamination and provided limited biological insights, to become a fully genomic discipline that is changing our conception of human history. Recent successes include the sequencing of extinct homini...

  11. Think Human

    DEFF Research Database (Denmark)

    Nielsen, Charlotte Marie Bisgaard

    2013-01-01

    years' campaigns suggests that the theory of communication underlying the campaign has its basis in mechanical action rather than in human communication. The practice of 'Communication design' is investigated in relation to this metaphorical 'machine thinking' model of communication and contrasted...... with the human-centered theory of communication advocated by integrationism....

  12. Human kapital

    DEFF Research Database (Denmark)

    Grosen, Anders; Nielsen, Peder Harbjerg

    2007-01-01

    finansiel og human kapital. Den traditionelle rådgivnings snævre synsvinkel kan føre til forkerte investeringsråd. Der skal derfor opfordres til, at de finansielle virksomheder i tilrettelæggelsen af deres rådgivning af private kunder systematisk inddrager den humane kapitals størrelse og karakteristika i...

  13. Human trichuriasis

    DEFF Research Database (Denmark)

    Betson, Martha; Søe, Martin Jensen; Nejsum, Peter

    2015-01-01

    Human trichuriasis is a neglected tropical disease which affects hundreds of millions of people worldwide and is particularly prevalent among children living in areas where sanitation is poor. This review examines the current knowledge on the taxonomy, genetics and phylogeography of human Trichuris...

  14. Placebo effect in clinical trial design for irritable bowel syndrome.

    Science.gov (United States)

    Shah, Eric; Pimentel, Mark

    2014-04-30

    Ongoing efforts to improve clinical trial design in irritable bowel syndrome have been hindered by high placebo response rates and ineffective outcome measures. We assessed established strategies to minimize placebo effect as well as the various ap-proaches to placebo effect which can affect trial design. These include genetic markers such as catechol-O-methyltransferase, opioidergic and dopaminergic neurobiologic theory, pre-cebo effect centered on expectancy theory, and side effect unblinding grounded on conditioning theory. We reviewed endpoints used in the study of IBS over the past decade including adequate relief and subjective global relief, emphasizing their weaknesses in fully evaluating the IBS condition, specifically their motility effects based on functional net value and relative benefit-harm based on dropouts due to adverse events. The focus of this review is to highlight ongoing efforts to improve clinical trial design which can lead to better outcomes in a real-world setting.

  15. Digital Humanities

    DEFF Research Database (Denmark)

    Brügger, Niels

    2016-01-01

    , and preserving material to study, as an object of study in its own right, as an analytical tool, or for collaborating, and for disseminating results. The term "digital humanities" was coined around 2001, and gained currency within academia in the following years. However, computers had been used within......Digital humanities is an umbrella term for theories, methodologies, and practices related to humanities scholarship that use the digital computer as an integrated and essential part of its research and teaching activities. The computer can be used for establishing, finding, collecting...

  16. Human Computation

    CERN Multimedia

    CERN. Geneva

    2008-01-01

    What if people could play computer games and accomplish work without even realizing it? What if billions of people collaborated to solve important problems for humanity or generate training data for computers? My work aims at a general paradigm for doing exactly that: utilizing human processing power to solve computational problems in a distributed manner. In particular, I focus on harnessing human time and energy for addressing problems that computers cannot yet solve. Although computers have advanced dramatically in many respects over the last 50 years, they still do not possess the basic conceptual intelligence or perceptual capabilities...

  17. MVP immunohistochemistry is a useful adjunct in distinguishing leiomyosarcoma from leiomyoma and leiomyoma with bizarre nuclei.

    Science.gov (United States)

    Lintel, Nicholas J; Luebker, Stephen A; Lele, Subodh M; Koepsell, Scott A

    2018-03-01

    Morphologically, distinguishing between leiomyoma (LM) and leiomyosarcoma (LMS) is not always straightforward, especially with benign variants such as bizarre leiomyoma (BLM). To identify potential markers of malignancy in uterine smooth muscle tumors, proteomic studies were performed followed by assessment of protein expression by immunohistochemistry. Archival formalin-fixed, paraffin-embedded tissues from tumors (n = 23) diagnosed as LM, BLM, and LMS (using published criteria) were selected for the study. Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry was applied to pooled samples of formalin-fixed, paraffin-embedded LM and LMS tumor tissue to assay the relative protein quantities and look for expression patterns differentiating the 2 tumor types. A total of 592 proteins were quantified, and 10 proteins were differentially expressed between LM and LMS. Select proteins were chosen for evaluation by immunohistochemistry (IHC) based on antibody availability and biologic relevance in the literature. IHC was performed on a tissue microarray, and intensity was evaluated using imaging software. Major vault protein (MVP) and catechol O-methyltransferase had 3.05 and 13.94 times higher expression in LMS relative to LM by sequential window acquisition of all theoretical fragment ion spectra mass spectrometry, respectively. By IHC, MVP (clone 1014; Santa Cruz Biotechnology, Dallas, TX) was found to be 50% sensitive and 100% specific when comparing LMS to LM. Catechol O-methyltransferase (clone FL-271; Santa Cruz Biotechnology) had a sensitivity of 38% and a specificity of 88%. Six of 7 BLM had expression of MVP similar to LM. Immunohistochemical staining for MVP is a useful adjunct in distinguishing LMS from LM and BLM in difficult cases. Copyright © 2018. Published by Elsevier Inc.

  18. Human expunction

    Science.gov (United States)

    Klee, Robert

    2017-10-01

    Thomas Nagel in `The Absurd' (Nagel 1971) mentions the future expunction of the human species as a `metaphor' for our ability to see our lives from the outside, which he claims is one source of our sense of life's absurdity. I argue that the future expunction (not to be confused with extinction) of everything human - indeed of everything biological in a terran sense - is not a mere metaphor but a physical certainty under the laws of nature. The causal processes by which human expunction will take place are presented in some empirical detail, so that philosophers cannot dismiss it as merely speculative. I also argue that appeals to anthropic principles or to forms of mystical cosmology are of no plausible avail in the face of human expunction under the laws of physics.

  19. Human Cloning

    National Research Council Canada - National Science Library

    Johnson, Judith A; Williams, Erin D

    2006-01-01

    .... Scientists in other labs, including Harvard University and the University of California at San Francisco, intend to produce cloned human embryos in order to derive stem cells for medical research...

  20. Human brucellosis

    NARCIS (Netherlands)

    Franco, María Pía; Mulder, Maximilian; Gilman, Robert H.; Smits, Henk L.

    2007-01-01

    Human brucellosis still presents scientists and clinicians with several challenges, such as the understanding of pathogenic mechanisms of Brucella spp, the identification of markers for disease severity, progression, and treatment response, and the development of improved treatment regimens.

  1. Human settlements

    CSIR Research Space (South Africa)

    Van Niekerk, Cornelia W

    2017-09-01

    Full Text Available risk of deaths and injuries by drowning in floods and migration- related health effects. • Increased migration, which can result in human suffering, human rights violations, conflicts and political instability. • Loss of property and livelihoods.... The vulnerability of settlements in southern Africa is impacted by various and complex socio-economic processes related to the cultural, political and institutional contexts and demographic pressure, as well as specific high-risk zones susceptible to flash floods...

  2. Human Cloning

    Science.gov (United States)

    2006-07-20

    Human Fertilization and Embryology Authority (HFEA). A team of scientists headed by Alison Murdoch at the University of Newcastle received permission...not yet reported success in isolating stem cells from a cloned human embryo. A research team headed by Ian Wilmut at the University of Edinburgh...research group, headed by Douglas Melton and Kevin Eggan, submitted their proposal to a Harvard committee composed of ethicists, scientists and public

  3. Human cognition

    International Nuclear Information System (INIS)

    Norman, D.A.

    1982-01-01

    The study of human cognition encompasses the study of all mental phenomena, from the receipt and interpretation of sensory information to the final control of the motor system in the performance of action. The cognitive scientist examines all intermediary processes, including thought, decision making, and memory and including the effects of motivation, states of arousal and stress, the study of language, and the effects of social factors. The field therefore ranges over an enormous territory, covering all that is known or that should be known about human behavior. It is not possible to summarize the current state of knowledge about cognition with any great confidence that we know the correct answer about any aspect of the work. Nontheless, models provide good characterizations of certain aspects of the data and situations. Even if these models should prove to be incorrect, they do provide good approximate descriptions of people's behavior in some situations, and these approximations will still apply even when the underlying theories have changed. A quick description is provided of models within a number of areas of human cognition and skill and some general theoretical frameworks with which to view human cognition. The frameworks are qualitative descriptions that provide a way to view the development of more detailed, quantitative models and, most important, a way of thinking about human performance and skill

  4. Beyond Humanisms

    OpenAIRE

    Capurro, Rafael

    2012-01-01

    In the first part of this paper a short history of Western humanisms (Socrates, Pico della Mirandola, Descartes, Kant) is presented. As far as these humanisms rest on a fixation of the ‘humanum’ they are metaphysical, although they might radically differ from each other. The second part deals with the present debate on trans- and posthumanism in the context of some breath-taking developments in science and technology.Angeletics, a theory of messengers and messages, intends to give an answer t...

  5. ASSOCIATION STUDY OF 5-HTR2A-1438A/G,COMTVAL158MET,MAOA-LPR,DATVNTR AND 5-HTTVNTR POLYMORPHISMS WITH COOCCURRENCE HEROIN DEPENDENCE AND ANTISOCIAL PERSONALITY DISORDERS IN MALES%5-HTR2A-1438A/G、COMTVal158Met、MAOA-LPR、5-HTTVNTR 、DATVNTR与男性海洛因依赖共患反社会性人格障碍的关联研究*

    Institute of Scientific and Technical Information of China (English)

    杨梅; 郝伟; 邬志美; 王文甫; 周旭辉; 姜国清; 汤美云; 黄健

    2010-01-01

    目的:探讨5-HTR2A受体基因(5-hydroxytryptamine receptor 2A gene,5-HTR2A)-1438A/G多态性(5-HTR2A-1438A/G,rs6311)、儿茶酚-O-甲基转移酶基因(catechol-O-methyltransferase gene,COMT)Val158Met多态性(COMTVal158Met,rs4680)、单胺氧化酶A基因(monoamine oxidase A gene,MAOA)启动子区可变数目串联重复序列(variable number of tandem repeats,VNTR) 多态性(称为MAOA多型变异区段,MAOA-linked polymorphic region,MAOA-LPR))、多巴胺转运体基因(dopamine transporter gene,DAT)外显子15靠近3′端的可变数目串联重复序列多态性(DATVNTR)、5-HT转运体基因(5-hydroxytryptamine transporter gene,5-HTT)内含子2内可变数目串联重复序列多态性(5-HTTVNTR)及以上各位点之间的交互作用与男性海洛因依赖共患反社会性人格障碍有无关联.方法:采用病历对照关联分析,应用聚合酶链式反应和连接酶检测反应(polymerase chain reaction-ligase detection reaction,PCR-LDR)技术检测588例男性海洛因依赖者(其中共患反社会性人格障碍者311例,不共患反社会性人格障碍者277例)和194例健康男性5-HTR2A-1438A/G、COMTVal158Met、MAOA-LPR、DATVNTR、5-HTTVNTR多态性的基因型,对各位点的基因型频率、等位基因频率及各位点之间的交互作用进行疾病关联分析.结果:共患反社会性人格障碍的男性海洛因依赖者与健康男性间,共患与不共患反社会性人格障碍的男性海洛因依赖者间在5-HTTVNTR的基因型和等位基因频率上均有统计学差异,携带10次重复序列(10-repeats,10R)等位基因的个体共患海洛因依赖和反社会性人格障碍风险相对较大.经MDR分析,在男性海洛因依赖者中,HTTVNTR与DATVNTR的二因模型子对反社会性人格障碍的预测准确度最大,符号检验有统计学差异,校正后P值为0.067,接近显著性差异.携带5-HTTVNTR等位基因10R和/或携带DATVNTR等位基因9R的个体共患反社会性人格障碍的风

  6. Human Parechoviruses

    DEFF Research Database (Denmark)

    Fischer, Thea Kølsen; Harvala, Heli; Midgley, Sofie

    2017-01-01

    Infections with human parechoviruses (HPeV) are highly prevalent, particularly in neonates, where they may cause substantial morbidity and mortality. The clinical presentation of HPeV infection is often indistinguishable from that of enterovirus (EV) infection and may vary from mild disease...

  7. Practicing Humanities

    DEFF Research Database (Denmark)

    Gimmler, Antje

    2016-01-01

    and self-reflective democracy. Contemporary humanities have adopted a new orientation towards practices, and it is not clear how this fits with the ideals of ‘Bildung’ and ‘pure science’. A possible theoretical framework for this orientation towards practices could be found in John Dewey’s pragmatic...

  8. Human waste

    NARCIS (Netherlands)

    Amin, Md Nurul; Kroeze, Carolien; Strokal, Maryna

    2017-01-01

    Many people practice open defecation in south Asia. As a result, lot of human waste containing nutrients such as nitrogen (N) and phosphorus (P) enter rivers. Rivers transport these nutrients to coastal waters, resulting in marine pollution. This source of nutrient pollution is, however, ignored in

  9. Human Trafficking

    Science.gov (United States)

    Wilson, David McKay

    2011-01-01

    The shadowy, criminal nature of human trafficking makes evaluating its nature and scope difficult. The U.S. State Department and anti-trafficking groups estimate that worldwide some 27 million people are caught in a form of forced servitude today. Public awareness of modern-day slavery is gaining momentum thanks to new abolitionist efforts. Among…

  10. Think Human

    DEFF Research Database (Denmark)

    Nielsen, Charlotte Marie Bisgaard

    2013-01-01

    years' campaigns suggests that the theory of communication underlying the campaign has its basis in mechanical action rather than in human communication. The practice of 'Communication design' is investigated in relation to this metaphorical 'machine thinking' model of communication and contrasted...

  11. Nothing Human

    Science.gov (United States)

    Wharram, C. C.

    2014-01-01

    In this essay C. C. Wharram argues that Terence's concept of translation as a form of "contamination" anticipates recent developments in philosophy, ecology, and translation studies. Placing these divergent fields of inquiry into dialogue enables us read Terence's well-known statement "I am a human being--I deem nothing…

  12. Human Rights and Human Function

    Directory of Open Access Journals (Sweden)

    Mohsen Javadi

    2006-03-01

    Full Text Available This paper firstly explores some theories of Human Rights justification and then assents to the theory that Human Rights is based on justified moral values. In order to justify moral values, Aristotle’s approach called “Function Argument” is reviewed. Propounding this argument, the writer attempts to show that all analysis of human identity will directly contribute to the man’s view of his rights. Not only Human rights is really determined by human function or human distinguishing characteristic i.e. human identity, but in the world of knowledge the proper method to know human rights is to know human being himself. n cloning violates man’s rights due to two reasons: damage of human identity and violation of the right to be unique. Attempting to clarify the nature of human cloning, this article examines the aspects to be claimed to violate human rights and evaluates the strength of the reasons for this claim. این مقاله پس از بررسی اجمالی برخی از نظریه‌های توجیه حقوق بشر، نظریة ابتنای آن بر ارزش‌های اخلاقی موجّه را می‌پذیرد. دربارة چگونگی توجیه ارزش اخلاقی، رویکرد ارسطو که به «برهان ارگن» موسوم است، مورد بحث و بررسی قرار می‌گیرد. مؤلف با طرح این برهان می‌کوشد نشان دهد ارائه هرگونه تحلیل از هویت انسان در نگرش آدمی به حقوق خود تأثیر مستقیم خواهد گذاشت. حقوق آدمی نه فقط از ناحیة کارویژه یا فصل ممیز وی (هویت انسان تعیّن واقعی می‌گیرد، بلکه در عالم معرفت هم راه درست شناخت حقوق بشر، شناخت خود انسان است.

  13. Human Rights, Human Needs, Human Development, Human Security : Relationships between four international 'human' discourses

    NARCIS (Netherlands)

    D.R. Gasper (Des)

    2007-01-01

    textabstractHuman rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and politics; each

  14. Human Face as human single identity

    OpenAIRE

    Warnars, Spits

    2014-01-01

    Human face as a physical human recognition can be used as a unique identity for computer to recognize human by transforming human face with face algorithm as simple text number which can be primary key for human. Human face as single identity for human will be done by making a huge and large world centre human face database, where the human face around the world will be recorded from time to time and from generation to generation. Architecture database will be divided become human face image ...

  15. Human Rights in the Humanities

    Science.gov (United States)

    Harpham, Geoffrey

    2012-01-01

    Human rights are rapidly entering the academic curriculum, with programs appearing all over the country--including at Duke, Harvard, Northeastern, and Stanford Universities; the Massachusetts Institute of Technology; the Universities of Chicago, of Connecticut, of California at Berkeley, and of Minnesota; and Trinity College. Most of these…

  16. Human reliability

    International Nuclear Information System (INIS)

    Bubb, H.

    1992-01-01

    This book resulted from the activity of Task Force 4.2 - 'Human Reliability'. This group was established on February 27th, 1986, at the plenary meeting of the Technical Reliability Committee of VDI, within the framework of the joint committee of VDI on industrial systems technology - GIS. It is composed of representatives of industry, representatives of research institutes, of technical control boards and universities, whose job it is to study how man fits into the technical side of the world of work and to optimize this interaction. In a total of 17 sessions, information from the part of ergonomy dealing with human reliability in using technical systems at work was exchanged, and different methods for its evaluation were examined and analyzed. The outcome of this work was systematized and compiled in this book. (orig.) [de

  17. Human paleoneurology

    CERN Document Server

    2015-01-01

    The book presents an integrative review of paleoneurology, the study of endocranial morphology in fossil species. The main focus is on showing how computed methods can be used to support advances in evolutionary neuroanatomy, paleoanthropology and archaeology and how they have contributed to creating a completely new perspective in cognitive neuroscience. Moreover, thanks to its multidisciplinary approach, the book addresses students and researchers approaching human paleoneurology from different angles and for different purposes, such as biologists, physicians, anthropologists, archaeologists

  18. Human universe

    CERN Document Server

    Cox, Brian

    2014-01-01

    Human life is a staggeringly strange thing. On the surface of a ball of rock falling around a nuclear fireball in the blackness of a vacuum the laws of nature conspired to create a naked ape that can look up at the stars and wonder where it came from. What is a human being? Objectively, nothing of consequence. Particles of dust in an infinite arena, present for an instant in eternity. Clumps of atoms in a universe with more galaxies than people. And yet a human being is necessary for the question itself to exist, and the presence of a question in the universe - any question - is the most wonderful thing. Questions require minds, and minds bring meaning. What is meaning? I don't know, except that the universe and every pointless speck inside it means something to me. I am astonished by the existence of a single atom, and find my civilisation to be an outrageous imprint on reality. I don't understand it. Nobody does, but it makes me smile. This book asks questions about our origins, our destiny, and our place i...

  19. Introduction: Digital Humanities, Public Humanities

    Directory of Open Access Journals (Sweden)

    Alex Christie

    2014-07-01

    Full Text Available NANO: New American Notes Online: An Interdisciplinary Academic Journal for Big Ideas in a Small World. This special issue shows how both public and digital humanities research can be rendered more persuasive through engagement with cultures beyond the academy. More specifically, the aim of this special issue is to demonstrate how investments in technologies and computation are not necessarily antithetical to investments in critical theory and social justice.

  20. Human Capital, (Human) Capabilities and Higher Education

    Science.gov (United States)

    Le Grange, L.

    2011-01-01

    In this article I initiate a debate into the (de)merits of human capital theory and human capability theory and discuss implications of the debate for higher education. Human capital theory holds that economic growth depends on investment in education and that economic growth is the basis for improving the quality of human life. Human capable…

  1. Humanizing Architecture

    DEFF Research Database (Denmark)

    Toft, Tanya Søndergaard

    2015-01-01

    The article proposes the urban digital gallery as an opportunity to explore the relationship between ‘human’ and ‘technology,’ through the programming of media architecture. It takes a curatorial perspective when proposing an ontological shift from considering media facades as visual spectacles...... agency and a sense of being by way of dematerializing architecture. This is achieved by way of programming the symbolic to provide new emotional realizations and situations of enlightenment in the public audience. This reflects a greater potential to humanize the digital in media architecture....

  2. Humanized mouse models: Application to human diseases.

    Science.gov (United States)

    Ito, Ryoji; Takahashi, Takeshi; Ito, Mamoru

    2018-05-01

    Humanized mice are superior to rodents for preclinical evaluation of the efficacy and safety of drug candidates using human cells or tissues. During the past decade, humanized mouse technology has been greatly advanced by the establishment of novel platforms of genetically modified immunodeficient mice. Several human diseases can be recapitulated using humanized mice due to the improved engraftment and differentiation capacity of human cells or tissues. In this review, we discuss current advanced humanized mouse models that recapitulate human diseases including cancer, allergy, and graft-versus-host disease. © 2017 Wiley Periodicals, Inc.

  3. Human steroidogenesis

    DEFF Research Database (Denmark)

    Andersen, Claus Y; Ezcurra, Diego

    2014-01-01

    In the menstrual cycle, the mid-cycle surge of gonadotropins (both luteinising hormone [LH] and follicle-stimulating hormone [FSH]) signals the initiation of the periovulatory interval, during which the follicle augments progesterone production and begins to luteinise, ultimately leading to the r......In the menstrual cycle, the mid-cycle surge of gonadotropins (both luteinising hormone [LH] and follicle-stimulating hormone [FSH]) signals the initiation of the periovulatory interval, during which the follicle augments progesterone production and begins to luteinise, ultimately leading...... reviews current knowledge of the regulation of progesterone in the human ovary during the follicular phase and highlights areas where knowledge remains limited. In this review, we provide in-depth information outlining the regulation and function of gonadotropins in the complicated area of steroidogenesis...

  4. NATO Human View Architecture and Human Networks

    Science.gov (United States)

    Handley, Holly A. H.; Houston, Nancy P.

    2010-01-01

    The NATO Human View is a system architectural viewpoint that focuses on the human as part of a system. Its purpose is to capture the human requirements and to inform on how the human impacts the system design. The viewpoint contains seven static models that include different aspects of the human element, such as roles, tasks, constraints, training and metrics. It also includes a Human Dynamics component to perform simulations of the human system under design. One of the static models, termed Human Networks, focuses on the human-to-human communication patterns that occur as a result of ad hoc or deliberate team formation, especially teams distributed across space and time. Parameters of human teams that effect system performance can be captured in this model. Human centered aspects of networks, such as differences in operational tempo (sense of urgency), priorities (common goal), and team history (knowledge of the other team members), can be incorporated. The information captured in the Human Network static model can then be included in the Human Dynamics component so that the impact of distributed teams is represented in the simulation. As the NATO militaries transform to a more networked force, the Human View architecture is an important tool that can be used to make recommendations on the proper mix of technological innovations and human interactions.

  5. The Digital Humanities as a Humanities Project

    Science.gov (United States)

    Svensson, Patrik

    2012-01-01

    This article argues that the digital humanities can be seen as a humanities project in a time of significant change in the academy. The background is a number of scholarly, educational and technical challenges, the multiple epistemic traditions linked to the digital humanities, the potential reach of the field across and outside the humanities,…

  6. The downside of strong emotional memories: how human memory-related genes influence the risk for posttraumatic stress disorder--a selective review.

    Science.gov (United States)

    Wilker, Sarah; Elbert, Thomas; Kolassa, Iris-Tatjana

    2014-07-01

    A good memory for emotionally arousing experiences may be intrinsically adaptive, as it helps the organisms to predict safety and danger and to choose appropriate responses to prevent potential harm. However, under conditions of repeated exposure to traumatic stressors, strong emotional memories of these experiences can lead to the development of trauma-related disorders such as posttraumatic stress disorder (PTSD). This syndrome is characterized by distressing intrusive memories that can be so intense that the survivor is unable to discriminate past from present experiences. This selective review on the role of memory-related genes in PTSD etiology is divided in three sections. First, we summarize studies indicating that the likelihood to develop PTSD depends on the cumulative exposure to traumatic stressors and on individual predisposing risk factors, including a substantial genetic contribution to PTSD risk. Second, we focus on memory processes supposed to be involved in PTSD etiology and present evidence for PTSD-associated alterations in both implicit (fear conditioning, fear extinction) and explicit memory for emotional material. This is supplemented by a brief description of structural and functional alterations in memory-relevant brain regions in PTSD. Finally, we summarize a selection of studies indicating that genetic variations found to be associated with enhanced fear conditioning, reduced fear extinction or better episodic memory in human experimental studies can have clinical implications in the case of trauma exposure and influence the risk of PTSD development. Here, we focus on genes involved in noradrenergic (ADRA2B), serotonergic (SLC6A4), and dopaminergic signaling (COMT) as well as in the molecular cascades of memory formation (PRKCA and WWC1). This is supplemented by initial evidence that such memory-related genes might also influence the response rates of exposure-based psychotherapy or pharmacological treatment of PTSD, which underscores the

  7. Managing the Human in Human Brands

    Directory of Open Access Journals (Sweden)

    Fournier Susan

    2018-05-01

    Full Text Available The physical and social realities, mental biases and limitations of being human differentiate human brands from others. It is their very humanness that introduces risk while generating the ability for enhanced returns. Four particular human characteristics can create imbalance or inconsistency between the person and the brand: mortality, hubris, unpredictability and social embeddedness. None of these qualities manifest in traditional non-human brands, and all of them present risks requiring active managerial attention. Rather than treating humans as brands and making humans into brands for sale in the commercial marketplace, our framework forces a focus on keeping a balance between the person and the personified object.

  8. Human cloning and human dignity

    Directory of Open Access Journals (Sweden)

    Hasan Eslami

    2006-12-01

    Full Text Available Catholic Church and most of Muslims believe that human cloning is in contrast with human rights. They argue that applying Somatic Nuclear Transfer Technique or so-called cloning to humans is against human dignity. Their main reason is that the cloned person would be a copy or shadow of another person and lack his or her identity and uniqueness. They also argue that in the process of cloning human beings would be treated as laboratory mice. This article tries to evaluate this kind of argumentation and shows that the "human dignity" expression in the relevant writings is vague and has been used inappropriately. مسیحیان و برخی از مسلمانان استدلال می‌کنند که کاربست تکنیک شبیه‌سازی ناقض کرامت انسانی است. این دلیل خود به صورت‌های مختلفی بیان می‌شود، مانند آنکه انسان موضوع آزمایش‌های علمی قرار می‌گیرد و با او مانند حیوانات رفتار می‌شود. گاه نیز تغییر نحوة تولید مثل، مایة نقض کرامت انسانی قلمداد می‌گردد و گاه به مسئلة از بین رفتن هویت فردی اشاره می‌شود. نگارنده در دو قسمت، دیدگاه مسیحیان و مسلمانان را در این باره نقل و تحلیل کرده است و کوشیده است نشان دهد که استناد به مفهوم کرامت انسانی در این جا مبهم و ناگویاست و مخالفان کوشش دقیقی در جهت تبیین دلیل خود به عمل نیاورده‌اند.

  9. Digital Humanities

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørn

    2015-01-01

    overgangen fra trykkekultur til digital kultur. For det første problemstillingen omkring digitalisering af litterær kulturarv med fokus på kodning og tagging af teksten samt organisering i hypertekststrukturer. For det andet reorganiseringen af det digitale dokument i dataelementer og database. For det......Artiklen præsenterer først nogle generelle problemstillinger omkring Digital Humanities (DH) med det formål at undersøge dem nærmere i relation til konkrete eksempler på forskellige digitaliseringsmåder og ændringer i dokumentproduktion. I en nærmere afgrænsning vælger artiklen den tendens i DH......, der betragter DH som forbundet med "making" og "building" af digitale objekter og former. Dette kan også karakteriseres som DH som praktisk-produktiv vending. Artiklen har valgt tre typer af digitalisering. De er valgt ud fra, at de skal repræsentere forskellige måder at håndtere digitaliseringen på...

  10. Modern Human Engineering

    International Nuclear Information System (INIS)

    Jeong, Byeong Yong; Lee Dong Kyeong

    2005-08-01

    These are the titles of each chapter. They are as in the following; design of human-centerdness, human machine system, information processing process, sense of human, user interface, elements of human body, vital dynamics, measurement of reaction of human body, estimation and management of working environment, mental characteristic of human, human error, group, organization and leadership, safety supervision, process analysis, time studying, work sampling, work factor and methods time measurement, introduction of muscular skeletal disease and program of preventive management.

  11. Modern Human Engineering

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Byeong Yong; Lee Dong Kyeong

    2005-08-15

    These are the titles of each chapter. They are as in the following; design of human-centerdness, human machine system, information processing process, sense of human, user interface, elements of human body, vital dynamics, measurement of reaction of human body, estimation and management of working environment, mental characteristic of human, human error, group, organization and leadership, safety supervision, process analysis, time studying, work sampling, work factor and methods time measurement, introduction of muscular skeletal disease and program of preventive management.

  12. HUMANISM OF ANTROPOCENTRISM AND ANTROPOCENTRISM WITHOUT HUMANISM

    Directory of Open Access Journals (Sweden)

    N. S. Shilovskaya

    2014-01-01

    Full Text Available Article is devoted to the distinction of humanism and anthropocentrism which is based on the parity of the person and being. Genetic communication of humanism and anthropocentrism and their historical break comes to light.

  13. Superintelligence, Humans, and War

    Science.gov (United States)

    2015-04-13

    Recent studies of the human mind debunk the myth that humans only use 10-20 percent of the human mind. A healthy human mind uses up to 90 percent...way. They will eat what is in front of them to satiate their appetite not knowing if there is anymore food for the future. Humans can predict

  14. The golden triangle of human dignity: human security, human development and human rights

    NARCIS (Netherlands)

    Gaay Fortman, B. de

    2004-01-01

    The success or failure of processes of democratization cannot be detached from processes of development related to the aspirations of people at the grassroots. Human rights, in a more theoretical terminology, require human development in order to enhance human security.

  15. Human factors in training

    International Nuclear Information System (INIS)

    Dutton, J.W.; Brown, W.R.

    1981-01-01

    The Human Factors concept is a focused effort directed at those activities which require human involvement. Training is, by its nature, an activity totally dependent on the Human Factor. This paper identifies several concerns significant to training situations and discusses how Human Factor awareness can increase the quality of learning. Psychology in the training arena is applied Human Factors. Training is a method of communication represented by sender, medium, and receiver. Two-thirds of this communications model involves the human element directly

  16. Human-machine interactions

    Science.gov (United States)

    Forsythe, J Chris [Sandia Park, NM; Xavier, Patrick G [Albuquerque, NM; Abbott, Robert G [Albuquerque, NM; Brannon, Nathan G [Albuquerque, NM; Bernard, Michael L [Tijeras, NM; Speed, Ann E [Albuquerque, NM

    2009-04-28

    Digital technology utilizing a cognitive model based on human naturalistic decision-making processes, including pattern recognition and episodic memory, can reduce the dependency of human-machine interactions on the abilities of a human user and can enable a machine to more closely emulate human-like responses. Such a cognitive model can enable digital technology to use cognitive capacities fundamental to human-like communication and cooperation to interact with humans.

  17. The Human/Machine Humanities: A Proposal

    Directory of Open Access Journals (Sweden)

    Ollivier Dyens

    2016-03-01

    Full Text Available What does it mean to be human in the 21st century? The pull of engineering on every aspect of our lives, the impact of machines on how we represent ourselves, the influence of computers on our understanding of free-will, individuality and species, and the effect of microorganisms on our behaviour are so great that one cannot discourse on humanity and humanities without considering their entanglement with technology and with the multiple new dimensions of reality that it opens up. The future of humanities should take into account AI, bacteria, software, viruses (both organic and inorganic, hardware, machine language, parasites, big data, monitors, pixels, swarms systems and the Internet. One cannot think of humanity and humanities as distinct from technology anymore.

  18. Special Section: Human Rights

    Science.gov (United States)

    Frydenlund, Knut; And Others

    1978-01-01

    Eleven articles examine human rights in Europe. Topics include unemployment, human rights legislation, role of the Council of Europe in promoting human rights, labor unions, migrant workers, human dignity in industralized societies, and international violence. Journal available from Council of Europe, Directorate of Press and Information, 67006…

  19. Human factor reliability program

    International Nuclear Information System (INIS)

    Knoblochova, L.

    2017-01-01

    The human factor's reliability program was at Slovenske elektrarne, a.s. (SE) nuclear power plants. introduced as one of the components Initiatives of Excellent Performance in 2011. The initiative's goal was to increase the reliability of both people and facilities, in response to 3 major areas of improvement - Need for improvement of the results, Troubleshooting support, Supporting the achievement of the company's goals. The human agent's reliability program is in practice included: - Tools to prevent human error; - Managerial observation and coaching; - Human factor analysis; -Quick information about the event with a human agent; -Human reliability timeline and performance indicators; - Basic, periodic and extraordinary training in human factor reliability(authors)

  20. Economics of human trafficking.

    Science.gov (United States)

    Wheaton, Elizabeth M; Schauer, Edward J; Galli, Thomas V

    2010-01-01

    Because freedom of choice and economic gain are at the heart of productivity, human trafficking impedes national and international economic growth. Within the next 10 years, crime experts expect human trafficking to surpass drug and arms trafficking in its incidence, cost to human well-being, and profitability to criminals (Schauer and Wheaton, 2006: 164-165). The loss of agency from human trafficking as well as from modern slavery is the result of human vulnerability (Bales, 2000: 15). As people become vulnerable to exploitation and businesses continually seek the lowest-cost labour sources, trafficking human beings generates profit and a market for human trafficking is created. This paper presents an economic model of human trafficking that encompasses all known economic factors that affect human trafficking both across and within national borders. We envision human trafficking as a monopolistically competitive industry in which traffickers act as intermediaries between vulnerable individuals and employers by supplying differentiated products to employers. In the human trafficking market, the consumers are employers of trafficked labour and the products are human beings. Using a rational-choice framework of human trafficking we explain the social situations that shape relocation and working decisions of vulnerable populations leading to human trafficking, the impetus for being a trafficker, and the decisions by employers of trafficked individuals. The goal of this paper is to provide a common ground upon which policymakers and researchers can collaborate to decrease the incidence of trafficking in humans.

  1. Boundaries of Humanities: Writing Medical Humanities

    Science.gov (United States)

    Bolton, Gillie

    2008-01-01

    Literature and medicine is a discipline within medical humanities, which challenges medicine to reconfigure its scientific model to become interdisciplinary, and be disciplined by arts and humanities as well as science. The psychological, emotional, spiritual and physical are inextricably linked in people, inevitably entailing provisionality,…

  2. Human algorithmic stability and human Rademacher complexity

    NARCIS (Netherlands)

    Vahdat, Mehrnoosh; Oneto, L.; Ghio, A; Anguita, D.; Funk, M.; Rauterberg, G.W.M.

    2015-01-01

    In Machine Learning (ML), the learning process of an algo- rithm given a set of evidences is studied via complexity measures. The way towards using ML complexity measures in the Human Learning (HL) domain has been paved by a previous study, which introduced Human Rademacher Complexity (HRC): in this

  3. Human errors and mistakes

    International Nuclear Information System (INIS)

    Wahlstroem, B.

    1993-01-01

    Human errors have a major contribution to the risks for industrial accidents. Accidents have provided important lesson making it possible to build safer systems. In avoiding human errors it is necessary to adapt the systems to their operators. The complexity of modern industrial systems is however increasing the danger of system accidents. Models of the human operator have been proposed, but the models are not able to give accurate predictions of human performance. Human errors can never be eliminated, but their frequency can be decreased by systematic efforts. The paper gives a brief summary of research in human error and it concludes with suggestions for further work. (orig.)

  4. Defense Human Resources Activity > PERSEREC

    Science.gov (United States)

    Skip to main content (Press Enter). Toggle navigation Defense Human Resources Activity Search Search Defense Human Resources Activity: Search Search Defense Human Resources Activity: Search Defense Human Resources Activity U.S. Department of Defense Defense Human Resources Activity Overview

  5. Is less really more: Does a prefrontal efficiency genotype actually confer better performance when working memory becomes difficult?

    Science.gov (United States)

    Ihne, Jessica L; Gallagher, Natalie M; Sullivan, Marie; Callicott, Joseph H; Green, Adam E

    2016-01-01

    Perhaps the most widely studied effect to emerge from the combination of neuroimaging and human genetics is the association of the COMT-Val(108/158)Met polymorphism with prefrontal activity during working memory. COMT-Val is a putative risk factor in schizophrenia, which is characterized by disordered prefrontal function. Work in healthy populations has sought to characterize mechanisms by which the valine (Val) allele may lead to disadvantaged prefrontal cognition. Lower activity in methionine (Met) carriers has been interpreted as advantageous neural efficiency. Notably, however, studies reporting COMT effects on neural efficiency have generally not reported working memory performance effects. Those studies have employed relatively low/easy working memory loads. Higher loads are known to elicit individual differences in working memory performance that are not visible at lower loads. If COMT-Met confers greater neural efficiency when working memory is easy, a reasonable prediction is that Met carriers will be better able to cope with increasing demand for neural resources when working memory becomes difficult. To our knowledge, this prediction has thus far gone untested. Here, we tested performance on three working memory tasks. Performance on each task was measured at multiple levels of load/difficulty, including loads more demanding than those used in prior studies. We found no genotype-by-load interactions or main effects of COMT genotype on accuracy or reaction time. Indeed, even testing for performance differences at each load of each task failed to find a single significant effect of COMT genotype. Thus, even if COMT genotype has the effects on prefrontal efficiency that prior work has suggested, such effects may not directly impact high-load working memory ability. The present findings accord with previous evidence that behavioral effects of COMT are small or nonexistent and, more broadly, with a growing consensus that substantial effects on phenotype will

  6. Evaluating human genetic diversity

    National Research Council Canada - National Science Library

    This book assesses the scientific value and merit of research on human genetic differences--including a collection of DNA samples that represents the whole of human genetic diversity--and the ethical...

  7. Human Exposure and Health

    Science.gov (United States)

    The ROE is divided into 5 themes: Air, Water, Land, Human Exposure and Health and Ecological Condition. From these themes, the report indicators address fundamental questions that the ROE attempts to answer. For human health there are 3 questions.

  8. ECONOMICS OF HUMAN RESOURCES

    Directory of Open Access Journals (Sweden)

    IOANA - JULIETA JOSAN

    2011-04-01

    Full Text Available The purpose of this paper is to analyze human resources in terms of quantitative and qualitative side with special focus on the human capital accumulation influence. The paper examines the human resources trough human capital accumulation in terms of modern theory of human resources, educational capital, health, unemployment and migration. The findings presented in this work are based on theoretical economy publications and data collected from research materials. Sources of information include: documents from organizations - the EUROSTAT, INSSE - studies from publications, books, periodicals, and the Internet. The paper describes and analyzes human resources characteristics, human resource capacities, social and economic benefits of human capital accumulation based on economy, and the government plans and policies on health, education and labor market.

  9. Human bites (image)

    Science.gov (United States)

    Human bites present a high risk of infection. Besides the bacteria which can cause infection, there is ... the wound extends below the skin. Anytime a human bite has broken the skin, seek medical attention.

  10. HPV (Human Papillomavirus)

    Science.gov (United States)

    ... Consumers Consumer Information by Audience For Women HPV (human papillomavirus) Share Tweet Linkedin Pin it More sharing ... Español In Chamorro In Urdu In Vietnamese HPV (human papillomavirus) is a sexually transmitted virus. It is ...

  11. Human Papillomavirus (HPV) Vaccine

    Science.gov (United States)

    Why get vaccinated?HPV vaccine prevents infection with human papillomavirus (HPV) types that are associated with cause ... at http://www.cdc.gov/hpv. HPV Vaccine (Human Papillomavirus) Information Statement. U.S. Department of Health and ...

  12. Human Parainfluenza Viruses

    Science.gov (United States)

    ... Search Form Controls Cancel Submit Search The CDC Human Parainfluenza Viruses (HPIVs) Note: Javascript is disabled or ... CDC.gov . Recommend on Facebook Tweet Share Compartir Human parainfluenza viruses (HPIVs) commonly cause respiratory illnesses in ...

  13. Human Use Index (Future)

    Data.gov (United States)

    U.S. Environmental Protection Agency — Human land uses may have major impacts on ecosystems, affecting biodiversity, habitat, air and water quality. The human use index (also known as U-index) is the...

  14. Human Use Index

    Data.gov (United States)

    U.S. Environmental Protection Agency — Human land uses may have major impacts on ecosystems, affecting biodiversity, habitat, air and water quality. The human use index (also known as U-index) is the...

  15. Human papillomavirus molecular biology.

    Science.gov (United States)

    Harden, Mallory E; Munger, Karl

    Human papillomaviruses are small DNA viruses with a tropism for squamous epithelia. A unique aspect of human papillomavirus molecular biology involves dependence on the differentiation status of the host epithelial cell to complete the viral lifecycle. A small group of these viruses are the etiologic agents of several types of human cancers, including oral and anogenital tract carcinomas. This review focuses on the basic molecular biology of human papillomaviruses. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Human Computer Music Performance

    OpenAIRE

    Dannenberg, Roger B.

    2012-01-01

    Human Computer Music Performance (HCMP) is the study of music performance by live human performers and real-time computer-based performers. One goal of HCMP is to create a highly autonomous artificial performer that can fill the role of a human, especially in a popular music setting. This will require advances in automated music listening and understanding, new representations for music, techniques for music synchronization, real-time human-computer communication, music generation, sound synt...

  17. Humanities Review Journal

    African Journals Online (AJOL)

    Humanities Review Journal is published in June and December by Humanities Research Forum. The Journal publishes original, well-researched papers, review essays, interviews, resume, and commentaries, which offer new insights into the various disciplines in the Humanities. The focus is on issues about Africa.

  18. Humanity at the Edge

    DEFF Research Database (Denmark)

    Svendsen, Mette N.; Gjødsbøl, Iben M.; Dam, Mie S.

    2017-01-01

    At the heart of anthropology and the social sciences lies a notion of human existence according to which humans and animals share the basic need for food, but only humans have the capacity for morality. Based on fieldwork in a pig laboratory, a neonatal intensive care unit (NICU), and a dementia ...

  19. Human Document Project

    NARCIS (Netherlands)

    de Vries, Jeroen; Abelmann, Leon; Manz, A; Elwenspoek, Michael Curt

    2012-01-01

    “The Human Document Project‿ is a project which tries to answer all of the questions related to preserving information about the human race for tens of generations of humans to come or maybe even for a future intelligence which can emerge in the coming thousands of years. This document mainly

  20. Esprit: A Humanities Magazine.

    Science.gov (United States)

    Parker, Donald G.; Capella, Barry John

    In March 1984, the first issue of "Esprit," a semi-annual humanities magazine for the 56 two-year colleges in New York State, was published. The magazine seeks to confront the apparent decline of student interest in the humanities, community doubts about the relevance of the humanities, and the seeming indifference to the special truths…

  1. A Human Rights Glossary.

    Science.gov (United States)

    Flowers, Nancy

    1998-01-01

    Presents a human rights glossary that includes definitions of basic terms, treaties, charters, and groups/organizations that have been featured in previous articles in this edition of "Update on Law-Related Education"; the human rights terms have been compiled as part of the celebration of the Universal Declaration of Human Rights…

  2. Has Human Evolution Stopped?

    Directory of Open Access Journals (Sweden)

    Alan R. Templeton

    2010-07-01

    Full Text Available It has been argued that human evolution has stopped because humans now adapt to their environment via cultural evolution and not biological evolution. However, all organisms adapt to their environment, and humans are no exception. Culture defines much of the human environment, so cultural evolution has actually led to adaptive evolution in humans. Examples are given to illustrate the rapid pace of adaptive evolution in response to cultural innovations. These adaptive responses have important implications for infectious diseases, Mendelian genetic diseases, and systemic diseases in current human populations. Moreover, evolution proceeds by mechanisms other than natural selection. The recent growth in human population size has greatly increased the reservoir of mutational variants in the human gene pool, thereby enhancing the potential for human evolution. The increase in human population size coupled with our increased capacity to move across the globe has induced a rapid and ongoing evolutionary shift in how genetic variation is distributed within and among local human populations. In particular, genetic differences between human populations are rapidly diminishing and individual heterozygosity is increasing, with beneficial health effects. Finally, even when cultural evolution eliminates selection on a trait, the trait can still evolve due to natural selection on other traits. Our traits are not isolated, independent units, but rather are integrated into a functional whole, so selection on one trait can cause evolution to occur on another trait, sometimes with mildly maladaptive consequences.

  3. Human Machine Learning Symbiosis

    Science.gov (United States)

    Walsh, Kenneth R.; Hoque, Md Tamjidul; Williams, Kim H.

    2017-01-01

    Human Machine Learning Symbiosis is a cooperative system where both the human learner and the machine learner learn from each other to create an effective and efficient learning environment adapted to the needs of the human learner. Such a system can be used in online learning modules so that the modules adapt to each learner's learning state both…

  4. Skin and the non-human human

    DEFF Research Database (Denmark)

    Rösing, Lilian Munk

    2013-01-01

    The article puts forward an aesthetic and psychoanalytic analysis of Titian's painting, The Flaying of Marsyas, arguing that the painting is a reflection on the human subject as a being constituted by skin and by a core of non-humanity. The analysis is partly an answer to Melanie Hart's (2007) ar...... of the 'Muselmann', and Anton Ehrenzweig's psychoanalytic theory of artistic creation. Whereas Hart is focusing on form and colour, I also turn my attention towards the texture of the painting....

  5. Universe, human immortality and future human evaluation

    CERN Document Server

    Bolonkin, Alexander

    2011-01-01

    This book debates the universe, the development of new technologies in the 21st century and the future of the human race. Dr Bolonkin shows that a human soul is only the information in a person's head. He offers a new unique method for re-writing the main brain information in chips without any damage to the human brain. This is the scientific prediction of the non-biological (electronic) civilization and immortality of the human being. Such a prognosis is predicated upon a new law, discovered by the author, for the development of complex systems. According to this law, every self-copying system tends to be more complex than the previous system, provided that all external conditions remain the same. The consequences are disastrous: humanity will be replaced by a new civilization created by intellectual robots (which Dr Bolonkin refers to as "E-humans" and "E-beings"). These creatures, whose intellectual and mechanical abilities will far exceed those of man, will require neither food nor oxygen to sustain their...

  6. Modeling Human Leukemia Immunotherapy in Humanized Mice

    Directory of Open Access Journals (Sweden)

    Jinxing Xia

    2016-08-01

    Full Text Available The currently available human tumor xenograft models permit modeling of human cancers in vivo, but in immunocompromised hosts. Here we report a humanized mouse (hu-mouse model made by transplantation of human fetal thymic tissue plus hematopoietic stem cells transduced with a leukemia-associated fusion gene MLL-AF9. In addition to normal human lymphohematopoietic reconstitution as seen in non-leukemic hu-mice, these hu-mice showed spontaneous development of B-cell acute lymphoblastic leukemia (B-ALL, which was transplantable to secondary recipients with an autologous human immune system. Using this model, we show that lymphopenia markedly improves the antitumor efficacy of recipient leukocyte infusion (RLI, a GVHD-free immunotherapy that induces antitumor responses in association with rejection of donor chimerism in mixed allogeneic chimeras. Our data demonstrate the potential of this leukemic hu-mouse model in modeling leukemia immunotherapy, and suggest that RLI may offer a safe treatment option for leukemia patients with severe lymphopenia.

  7. Rethinking medical humanities.

    Science.gov (United States)

    Chiapperino, Luca; Boniolo, Giovanni

    2014-12-01

    This paper questions different conceptions of Medical Humanities in order to provide a clearer understanding of what they are and why they matter. Building upon former attempts, we defend a conception of Medical Humanities as a humanistic problem-based approach to medicine aiming at influencing its nature and practice. In particular, we discuss three main conceptual issues regarding the overall nature of this discipline: (i) a problem-driven approach to Medical Humanities; (ii) the need for an integration of Medical Humanities into medicine; (iii) the methodological requirements that could render Medical Humanities an effective framework for medical decision-making.

  8. [Human factors in medicine].

    Science.gov (United States)

    Lazarovici, M; Trentzsch, H; Prückner, S

    2017-01-01

    The concept of human factors is commonly used in the context of patient safety and medical errors, all too often ambiguously. In actual fact, the term comprises a wide range of meanings from human-machine interfaces through human performance and limitations up to the point of working process design; however, human factors prevail as a substantial cause of error in complex systems. This article presents the full range of the term human factors from the (emergency) medical perspective. Based on the so-called Swiss cheese model by Reason, we explain the different types of error, what promotes their emergence and on which level of the model error prevention can be initiated.

  9. Integrated Environmental Modelling: Human decisions, human challenges

    Science.gov (United States)

    Glynn, Pierre D.

    2015-01-01

    Integrated Environmental Modelling (IEM) is an invaluable tool for understanding the complex, dynamic ecosystems that house our natural resources and control our environments. Human behaviour affects the ways in which the science of IEM is assembled and used for meaningful societal applications. In particular, human biases and heuristics reflect adaptation and experiential learning to issues with frequent, sharply distinguished, feedbacks. Unfortunately, human behaviour is not adapted to the more diffusely experienced problems that IEM typically seeks to address. Twelve biases are identified that affect IEM (and science in general). These biases are supported by personal observations and by the findings of behavioural scientists. A process for critical analysis is proposed that addresses some human challenges of IEM and solicits explicit description of (1) represented processes and information, (2) unrepresented processes and information, and (3) accounting for, and cognizance of, potential human biases. Several other suggestions are also made that generally complement maintaining attitudes of watchful humility, open-mindedness, honesty and transparent accountability. These suggestions include (1) creating a new area of study in the behavioural biogeosciences, (2) using structured processes for engaging the modelling and stakeholder communities in IEM, and (3) using ‘red teams’ to increase resilience of IEM constructs and use.

  10. Human Respiratory Syncytial Virus and Human Metapneumovirus

    Directory of Open Access Journals (Sweden)

    Luciana Helena Antoniassi da Silva

    2009-08-01

    Full Text Available The human respiratory syncytial virus (hRSV and the human metapneumovírus (hMPV are main etiological agents of acute respiratory infections (ARI. The ARI is an important cause of childhood morbidity and mortality worldwide.  hRSV and hMPV are members of the Paramyxoviridae. They are enveloped, non-segmented viruses, with negative-sense single stranded genomes. Respiratory syncytial virus (hRSV is the best characterized agent viral of this group, associated with respiratory diseases in lower respiratory tract. Recently, a new human pathogen belonging to the subfamily Pneumovirinae was identified, the human metapneumovirus (hMPV, which is structurally similar to the hRSV, in genomic organization, viral structure, antigenicity and clinical symptoms.  The subfamily Pneumovirinae contains two genera: genus Pneumovirus contains hRSV, the bovine (bRSV, as well as the ovine and caprine respiratory syncytial virus and pneumonia virus of mice, the second genus Metapneumovirus, consists of avian metapneumovirus (aMPV and human metapneumovirus (hMPV. In this work, we present a brief narrative review of the literature on important aspects of the biology, epidemiology and clinical manifestations of infections by two respiratory viruses.

  11. Bursty human dynamics

    CERN Document Server

    Karsai, Márton; Kaski, Kimmo

    2018-01-01

    This book provides a comprehensive overview on emergent bursty patterns in the dynamics of human behaviour. It presents common and alternative understanding of the investigated phenomena, and points out open questions worthy of further investigations. The book is structured as follows. In the introduction the authors discuss the motivation of the field, describe bursty phenomena in case of human behaviour, and relate it to other disciplines. The second chapter addresses the measures commonly used to characterise heterogeneous signals, bursty human dynamics, temporal paths, and correlated behaviour. These definitions are first introduced to set the basis for the discussion of the third chapter about the observations of bursty human patterns in the dynamics of individuals, dyadic interactions, and collective behaviour. The subsequent fourth chapter discusses the models of bursty human dynamics. Various mechanisms have been proposed about the source of the heterogeneities in human dynamics, which leads to the in...

  12. The Human Cell Atlas.

    Science.gov (United States)

    Regev, Aviv; Teichmann, Sarah A; Lander, Eric S; Amit, Ido; Benoist, Christophe; Birney, Ewan; Bodenmiller, Bernd; Campbell, Peter; Carninci, Piero; Clatworthy, Menna; Clevers, Hans; Deplancke, Bart; Dunham, Ian; Eberwine, James; Eils, Roland; Enard, Wolfgang; Farmer, Andrew; Fugger, Lars; Göttgens, Berthold; Hacohen, Nir; Haniffa, Muzlifah; Hemberg, Martin; Kim, Seung; Klenerman, Paul; Kriegstein, Arnold; Lein, Ed; Linnarsson, Sten; Lundberg, Emma; Lundeberg, Joakim; Majumder, Partha; Marioni, John C; Merad, Miriam; Mhlanga, Musa; Nawijn, Martijn; Netea, Mihai; Nolan, Garry; Pe'er, Dana; Phillipakis, Anthony; Ponting, Chris P; Quake, Stephen; Reik, Wolf; Rozenblatt-Rosen, Orit; Sanes, Joshua; Satija, Rahul; Schumacher, Ton N; Shalek, Alex; Shapiro, Ehud; Sharma, Padmanee; Shin, Jay W; Stegle, Oliver; Stratton, Michael; Stubbington, Michael J T; Theis, Fabian J; Uhlen, Matthias; van Oudenaarden, Alexander; Wagner, Allon; Watt, Fiona; Weissman, Jonathan; Wold, Barbara; Xavier, Ramnik; Yosef, Nir

    2017-12-05

    The recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to identify all cell types in the human body. The Human Cell Atlas Project is an international collaborative effort that aims to define all human cell types in terms of distinctive molecular profiles (such as gene expression profiles) and to connect this information with classical cellular descriptions (such as location and morphology). An open comprehensive reference map of the molecular state of cells in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease. Here we describe the idea, its potential utility, early proofs-of-concept, and some design considerations for the Human Cell Atlas, including a commitment to open data, code, and community.

  13. Managing human performance

    International Nuclear Information System (INIS)

    Bishop, J.; LaRhette, R.

    1988-01-01

    Evaluating human error or human performance problems and correcting the root causes can help preclude recurrence. The Institute of Nuclear Power Operations (INPO), working with several members and participant utilities in an extended pilot program, has developed a nonpunitive program designed to identify, evaluate, and correct situations that cause human performance errors. The program is called the Human Performance Evaluation System (HPES). Its primary goal is to improve human reliability in overall nuclear plant operations by reducing human error through correction of the conditions that cause the errors. Workers at participating nuclear utilities are encouraged to report their errors and a specially trained plant coordinator investigates and recommends actions to correct the root causes of these errors

  14. Developing human technology curriculum

    Directory of Open Access Journals (Sweden)

    Teija Vainio

    2012-10-01

    Full Text Available During the past ten years expertise in human-computer interaction has shifted from humans interacting with desktop computers to individual human beings or groups of human beings interacting with embedded or mobile technology. Thus, humans are not only interacting with computers but with technology. Obviously, this shift should be reflected in how we educate human-technology interaction (HTI experts today and in the future. We tackle this educational challenge first by analysing current Master’s-level education in collaboration with two universities and second, discussing postgraduate education in the international context. As a result, we identified core studies that should be included in the HTI curriculum. Furthermore, we discuss some practical challenges and new directions for international HTI education.

  15. Human Respiratory Syncytial Virus and Human Metapneumovirus

    OpenAIRE

    Luciana Helena Antoniassi da Silva; Fernando Rosado Spilki; Adriana Gut Lopes Riccetto; Emilio Elias Baracat; Clarice Weis Arns

    2009-01-01

    The human respiratory syncytial virus (hRSV) and the human metapneumovírus (hMPV) are main etiological agents of acute respiratory infections (ARI). The ARI is an important cause of childhood morbidity and mortality worldwide.  hRSV and hMPV are members of the Paramyxoviridae. They are enveloped, non-segmented viruses, with negative-sense single stranded genomes. Respiratory syncytial virus (hRSV) is the best characterized agent viral of this group, associated with respiratory diseases in...

  16. Human intrusion: New ideas?

    International Nuclear Information System (INIS)

    Cooper, J.R.

    2002-01-01

    Inadvertent human intrusion has been an issue for the disposal of solid radioactive waste for many years. This paper discusses proposals for an approach for evaluating the radiological significance of human intrusion as put forward by ICRP with contribution from work at IAEA. The approach focuses on the consequences of the intrusion. Protective actions could, however, include steps to reduce the probability of human intrusion as well as the consequences. (author)

  17. Human reliability analysis

    International Nuclear Information System (INIS)

    Dougherty, E.M.; Fragola, J.R.

    1988-01-01

    The authors present a treatment of human reliability analysis incorporating an introduction to probabilistic risk assessment for nuclear power generating stations. They treat the subject according to the framework established for general systems theory. Draws upon reliability analysis, psychology, human factors engineering, and statistics, integrating elements of these fields within a systems framework. Provides a history of human reliability analysis, and includes examples of the application of the systems approach

  18. The human genome project

    International Nuclear Information System (INIS)

    Worton, R.

    1996-01-01

    The Human Genome Project is a massive international research project, costing 3 to 5 billion dollars and expected to take 15 years, which will identify the all the genes in the human genome - i.e. the complete sequence of bases in human DNA. The prize will be the ability to identify genes causing or predisposing to disease, and in some cases the development of gene therapy, but this new knowledge will raise important ethical issues

  19. Modern Human Capital Management

    OpenAIRE

    Feldberger, Madita

    2008-01-01

    Title: Modern Human Capital Management Seminar date: 30th of May 2008 Course: Master thesis in Business Administration, 15 ECTS Authors: Madita Feldberger Supervisor: Lars Svensson Keywords: Human capital, SWOT Analysis, Strategic Map, Balanced Scorecard Research Problem: Despite of the success of Human Capital Management (HCM) in research it did not arrive yet in the HR departments of many companies. Numerous firms even have problems to set their strategic goals with focus on HR. The HR Bala...

  20. Options for human intrusion

    International Nuclear Information System (INIS)

    Bauser, M.; Williams, R.

    1993-01-01

    This paper addresses options for dealing with human intrusion in terms of performance requirements and repository siting and design requirements. Options are presented, along with the advantages and disadvantages of certain approaches. At the conclusion, a conceptual approach is offered emphasizing both the minimization of subjective judgements concerning future human activity, and specification of repository requirements to minimize the likelihood of human intrusion and any resulting, harmful effects should intrusion occur

  1. Human Engineering Procedures Guide

    Science.gov (United States)

    1981-09-01

    Research Laboratory AFETR Air Force Eastern Test Range AFFTC Air Force Flight Test Center AFHRL Air Force Human Resources Laboratory AFR Air Force...performance requirements through the most effective use of man’s performance capability. 13 Human Engineering is one of five elements in the Human...applied judiciously and tailored to fit * the program or program phase and the acquisition strategy to achieve cost effective acquisition and life cycle

  2. Human babesiosis: Recent discoveries

    OpenAIRE

    Mitrović Sanja M.; Kranjčić-Zec Ivana F.; Arsić-Arsenijević Valentina S.; Džamić Aleksandar M.; Radonjić Ivana V.

    2004-01-01

    Introduction Babesiosis is caused by intraerythrocytic parasites of the genus Babesia, which is a common animal infection worldwide. This protozoa requires both a competent vertebrate and a nonvertebrate host (Ixodes sp. etc.) to maintain the transmission cycle. Human babesiosis Human babesiosis is predominantly caused by Babesia microti (rodent-borne piroplasm, an emerging zoonosis in humans in North America) and by Babesia divergens (bovine pathogen, in Europe). Occasionally, infection in A...

  3. Dogs catch human yawns

    OpenAIRE

    Joly-Mascheroni, Ramiro M; Senju, Atsushi; Shepherd, Alex J

    2008-01-01

    This study is the first to demonstrate that human yawns are possibly contagious to domestic dogs (Canis familiaris). Twenty-nine dogs observed a human yawning or making control mouth movements. Twenty-one dogs yawned when they observed a human yawning, but control mouth movements did not elicit yawning from any of them. The presence of contagious yawning in dogs suggests that this phenomenon is not specific to primate species and may indicate that dogs possess the capacity for a rudimentary f...

  4. Human Performance Research Center

    Data.gov (United States)

    Federal Laboratory Consortium — Biochemistry:Improvements in energy metabolism, muscular strength and endurance capacity have a basis in biochemical and molecular adaptations within the human body....

  5. Human spinal motor control

    DEFF Research Database (Denmark)

    Nielsen, Jens Bo

    2016-01-01

    Human studies in the past three decades have provided us with an emerging understanding of how cortical and spinal networks collaborate to ensure the vast repertoire of human behaviors. We differ from other animals in having direct cortical connections to spinal motoneurons, which bypass spinal...... the central motor command by opening or closing sensory feedback pathways. In the future, human studies of spinal motor control, in close collaboration with animal studies on the molecular biology of the spinal cord, will continue to document the neural basis for human behavior. Expected final online...

  6. Human Capital Overview

    National Research Council Canada - National Science Library

    McCarthy, Ellen E

    2007-01-01

    ...: To provide an agile, adaptive, integrated, and innovative defense intelligence workforce through a deliberate process identifying, implementing, and directing human capital organizational, doctrinal...

  7. Developing Human Resources through Actualizing Human Potential

    Science.gov (United States)

    Clarken, Rodney H.

    2012-01-01

    The key to human resource development is in actualizing individual and collective thinking, feeling and choosing potentials related to our minds, hearts and wills respectively. These capacities and faculties must be balanced and regulated according to the standards of truth, love and justice for individual, community and institutional development,…

  8. Challenges for Virtual Humans in Human Computing

    NARCIS (Netherlands)

    Reidsma, Dennis; Ruttkay, Z.M.; Huang, T; Nijholt, Antinus; Pantic, Maja; Pentland, A.

    The vision of Ambient Intelligence (AmI) presumes a plethora of embedded services and devices that all endeavor to support humans in their daily activities as unobtrusively as possible. Hardware gets distributed throughout the environment, occupying even the fabric of our clothing. The environment

  9. Human trafficking in Germany: strengthening victim's human rights

    OpenAIRE

    Follmar-Otto, Petra; Rabe, Heike

    2009-01-01

    The first study - "A human rights approach against human trafficking - International obligations and the status of implementation in Germany" - analyses how the prohibition of human trafficking and the resulting state obligations are anchored in human rights. The more recent specialised international agreements on human trafficking and law-making in the European Union are then presented. The emphasis is on the Council of Europe Convention, which professes to treat human trafficking in a human...

  10. Human Rights, History of

    NARCIS (Netherlands)

    de Baets, Antoon; Wright, James

    2015-01-01

    In this article, six basic debates about human rights are clarified from a historical perspective: the origin of human rights as moral rights connected to the natural law doctrine and opposed to positive rights; the wave of criticism of their abstract and absolute character by nineteenth-century

  11. Rationality in Human Movement.

    Science.gov (United States)

    O'Brien, Megan K; Ahmed, Alaa A

    2016-01-01

    It long has been appreciated that humans behave irrationally in economic decisions under risk: they fail to objectively consider uncertainty, costs, and rewards and instead exhibit risk-seeking or risk-averse behavior. We hypothesize that poor estimates of motor variability (influenced by motor task) and distorted probability weighting (influenced by relevant emotional processes) contribute to characteristic irrationality in human movement decisions.

  12. Human-centred Governance

    DEFF Research Database (Denmark)

    Bason, Christian

    2017-01-01

    Design approaches are now being applied all over the world as a powerful approach to innovating public policies and services. Christian Bason, author of Leading public design: Discovering human-centred governance, argues that by bringing design methods into play, public managers can lead change...... with citizens at the centre, and discover a new model for steering public organisations: human-centred governance....

  13. Translating the human microbiome

    NARCIS (Netherlands)

    Brown, J.; Vos, de W.M.; Distefano, P.S.; Doré, J.; Huttenhower, C.; Knight, R.; Lawley, T.D.; Raes, J.; Turnbaugh, P.

    2013-01-01

    Over the past decade, an explosion of descriptive analyses from initiatives, such as the Human Microbiome Project (HMP) and the MetaHIT project, have begun to delineate the human microbiome. Inhabitants of the intestinal tract, nasal passages, oral cavities, skin, gastrointestinal tract and

  14. Incorporating Human Interindividual Biotransformation ...

    Science.gov (United States)

    The protection of sensitive individuals within a population dictates that measures other than central tendencies be employed to estimate risk. The refinement of human health risk assessments for chemicals metabolized by the liver to reflect data on human variability can be accomplished through (1) the characterization of enzyme expression in large banks of human liver samples, (2) the employment of appropriate techniques for the quantification and extrapolation of metabolic rates derived in vitro, and (3) the judicious application of physiologically based pharmacokinetic (PBPK) modeling. While in vitro measurements of specific biochemical reactions from multiple human samples can yield qualitatively valuable data on human variance, such measures must be put into the perspective of the intact human to yield the most valuable predictions of metabolic differences among humans. For quantitative metabolism data to be the most valuable in risk assessment, they must be tied to human anatomy and physiology, and the impact of their variance evaluated under real exposure scenarios. For chemicals metabolized in the liver, the concentration of parent chemical in the liver represents the substrate concentration in the MichaelisMenten description of metabolism. Metabolic constants derived in vitro may be extrapolated to the intact liver, when appropriate conditions are met. Metabolic capacity Vmax; the maximal rate of the reaction) can be scaled directly to the concentration

  15. Human Powered Centrifuge

    Science.gov (United States)

    Mulenburg, Gerald M. (Inventor); Vernikos, Joan (Inventor)

    1997-01-01

    A human powered centrifuge has independently established turntable angular velocity and human power input. A control system allows excess input power to be stored as electric energy in a battery or dissipated as heat through a resistors. In a mechanical embodiment, the excess power is dissipated in a friction brake.

  16. Kinship and Human Evolution

    DEFF Research Database (Denmark)

    Bergendorff, Steen

    This book offers a exiting new explanation of human evolution. Based on insight from Anthropology is shows that human became 'cultured' beings capable of symbolic thought by developing rasting kinship based between groups that could not other wise survive in the harah climate condition during...

  17. Modeling human color categorization

    NARCIS (Netherlands)

    van den Broek, Egon; Schouten, Th.E.; Kisters, P.M.F.

    A unique color space segmentation method is introduced. It is founded on features of human cognition, where 11 color categories are used in processing color. In two experiments, human subjects were asked to categorize color stimuli into these 11 color categories, which resulted in markers for a

  18. Fungi that Infect Humans.

    Science.gov (United States)

    Köhler, Julia R; Hube, Bernhard; Puccia, Rosana; Casadevall, Arturo; Perfect, John R

    2017-06-01

    Fungi must meet four criteria to infect humans: growth at human body temperatures, circumvention or penetration of surface barriers, lysis and absorption of tissue, and resistance to immune defenses, including elevated body temperatures. Morphogenesis between small round, detachable cells and long, connected cells is the mechanism by which fungi solve problems of locomotion around or through host barriers. Secretion of lytic enzymes, and uptake systems for the released nutrients, are necessary if a fungus is to nutritionally utilize human tissue. Last, the potent human immune system evolved in the interaction with potential fungal pathogens, so few fungi meet all four conditions for a healthy human host. Paradoxically, the advances of modern medicine have made millions of people newly susceptible to fungal infections by disrupting immune defenses. This article explores how different members of four fungal phyla use different strategies to fulfill the four criteria to infect humans: the Entomophthorales, the Mucorales, the Ascomycota, and the Basidiomycota. Unique traits confer human pathogenic potential on various important members of these phyla: pathogenic Onygenales comprising thermal dimorphs such as Histoplasma and Coccidioides ; the Cryptococcus spp. that infect immunocompromised as well as healthy humans; and important pathogens of immunocompromised patients- Candida , Pneumocystis , and Aspergillus spp. Also discussed are agents of neglected tropical diseases important in global health such as mycetoma and paracoccidiomycosis and common pathogens rarely implicated in serious illness such as dermatophytes. Commensalism is considered, as well as parasitism, in shaping genomes and physiological systems of hosts and fungi during evolution.

  19. Global Journal of Humanities

    African Journals Online (AJOL)

    Journal Homepage Image. Global Journal of Humanities is aimed at promoting reasearch in all areas of Humanities including philosophy, languages, linguistics, literature, history, fine/applied arts, theater arts, architecture, etc. Visit the Global Journal Series website here: http://www.globaljournalseries.com/ ...

  20. Evaluating the Humanities

    Science.gov (United States)

    Brody, Howard

    2013-01-01

    How can one measure the value of teaching the humanities? The problem of assessment and accountability is prominent today, of course, in secondary and higher education. It is perhaps even more acute for those who teach the humanities in nontraditional settings, such as medical and other professional schools. The public assumes that academes can…

  1. Human gliomas contain morphine

    DEFF Research Database (Denmark)

    Olsen, Peter; Rasmussen, Mads; Zhu, Wei

    2005-01-01

    BACKGROUND: Morphine has been found in cancer cell lines originating from human and animal cells. Thus, it became important to demonstrate whether or not actual tumours contain this opiate alkaloid. MATERIAL/METHODS: Human glioma tissues were biochemically treated to isolate and separate endogenous...

  2. Human Resource Construction

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Centering on strategic objective of reform and development,CIAE formulated its objectives in human resource construction for the 13th Five-year Plan period,and achieved new apparent progress in human resource construction in 2015.1 Implementation of"LONGMA Project"

  3. Dynamics of human movement

    NARCIS (Netherlands)

    Koopman, Hubertus F.J.M.

    2010-01-01

    The part of (bio)mechanics that studies the interaction of forces on the human skeletal system and its effect on the resulting movement is called rigid body dynamics. Some basic concepts are presented: A mathematical formulation to describe human movement and how this relates on the mechanical loads

  4. Biodemography of human ageing

    DEFF Research Database (Denmark)

    Vaupel, James W

    2010-01-01

    Human senescence has been delayed by a decade. This finding, documented in 1994 and bolstered since, is a fundamental discovery about the biology of human ageing, and one with profound implications for individuals, society and the economy. Remarkably, the rate of deterioration with age seems...

  5. Human Intestinal Spirochaetosis

    NARCIS (Netherlands)

    Westerman, L.J.

    2013-01-01

    Human intestinal spirochaetosis is a condition of the colon that is characterized by the presence of spirochaetes attached to the mucosal cells of the colon. These spirochaetes belong to the family Brachyspiraceae and two species are known to occur in humans: Brachyspira aalborgi and Brachyspira

  6. Human migraine models

    DEFF Research Database (Denmark)

    Iversen, Helle Klingenberg

    2001-01-01

    , which is a human experience. A set-up for investigations of experimental headache and migraine in humans, has been evaluated and headache mechanisms explored by using nitroglycerin and other headache-inducing agents. Nitric oxide (NO) or other parts of the NO activated cascade seems to be responsible...

  7. Manage "Human Capital" Strategically

    Science.gov (United States)

    Odden, Allan

    2011-01-01

    To strategically manage human capital in education means restructuring the entire human resource system so that schools not only recruit and retain smart and capable individuals, but also manage them in ways that support the strategic directions of the organization. These management practices must be aligned with a district's education improvement…

  8. Introduction to human factors

    International Nuclear Information System (INIS)

    Winters, J.M.

    1988-03-01

    Some background is given on the field of human factors. The nature of problems with current human/computer interfaces is discussed, some costs are identified, ideal attributes of graceful system interfaces are outlined, and some reasons are indicated why it's not easy to fix the problems

  9. Teaching Human Rights Law.

    Science.gov (United States)

    Berman, Howard R.

    1985-01-01

    The international community has developed a system of human rights law relevant to many areas of legal encounter, which American law schools have been slow to incorporate into curricula. Teaching human rights law provides an opportunity for law schools to enrich the learning process and contribute creatively to the respect for rights in society.…

  10. Humane Education Projects Handbook.

    Science.gov (United States)

    Junior League of Ogden, UT.

    This handbook was developed to promote interest in humane education and to encourage the adoption of humane education projects. Although specifically designed to assist Junior Leagues in developing such projects, the content should prove valuable to animal welfare organizations, zoos, aquariums, nature centers, and other project-oriented groups…

  11. Human Mind Maps

    Science.gov (United States)

    Glass, Tom

    2016-01-01

    When students generate mind maps, or concept maps, the maps are usually on paper, computer screens, or a blackboard. Human Mind Maps require few resources and little preparation. The main requirements are space where students can move around and a little creativity and imagination. Mind maps can be used for a variety of purposes, and Human Mind…

  12. Urbanization and human rights

    NARCIS (Netherlands)

    Mihr, A.

    Urban governance on the basis of human rights can help to set up problem solving mechanisms to guarantee social peace, economic growth and political participation.If states both integrate more in international or regional human rights regime and give more autonomy to urban governments and local

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

    Science.gov (United States)

    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 mon...

  14. Schooling and Variation in the "COMT" Gene: The Devil Is in the Details

    Science.gov (United States)

    Campbell, Daniel; Bick, Johanna; Yrigollen, Carolyn M.; Lee, Maria; Joseph, Antony; Chang, Joseph T.; Grigorenko, Elena L.

    2013-01-01

    Background: Schooling is considered one of the major contributors to the development of intelligence within societies and individuals. Genetic variation might modulate the impact of schooling and explain, at least partially, the presence of individual differences in classrooms. Method: We studied a sample of 1,502 children (mean age = 11.7 years)…

  15. Burgundy-Franche-Comte Region. The energy transition commitment: for a positive-energy region

    International Nuclear Information System (INIS)

    2017-01-01

    This report first presents an inventory of actions and arrangement of the region for energy transition. These actions and arrangements first concern the mobilisation of territories. They also deal with buildings (social housing, public buildings, individual housing), and schools (actions on the built patrimony in terms of renovation, energy efficiency, renewable energies, and so on, implementation of a specific eco-school approach, and struggle against food waste in schools). They comprise some general means (through actions on public buildings, on vehicles), public purchases, transports (organisation and tariffs, access to stations, development of inter-modal and green transports, actions in favour of rural mobility, energy saving in touristic transport, development of car sharing, support to the development of tomorrow's vehicles). Other actions and arrangements concern the environment: waste reduction and management, development of circular economy, national scheme for biomass, education. Other themes are economy (support to sectors and enterprises), research and innovation, agriculture and forests, renewable energies, education and training, citizen mobilisation, digital environment. The presence and existence of various European programmes (FEDER, and others) in the region are mentioned

  16. The Human Technology

    DEFF Research Database (Denmark)

    Fausing, Bent

     Bent Fausing  "The Humane Technology", abstract (for The Two Cultures: Balancing Choices and Effects Oxford University July 20-26, 2008). The paper will investigate the use of technology in everyday aesthetics such as TV-commercials for mobile phones for Nokia, which slogan is, as it is well known......, "Nokia - connecting people". Which function does this technology get in narratives, images, interactions and affects here?      The mobile phone and its digital camera are depicted as being able to make a unique human presence and interaction. The medium, the technology is a necessary helper to get...... towards this very special and lost humanity. Without the technology, no special humanity is the prophecy. This personification or anthropomorphism is important for the branding of new technology. The technology is seen as creating a technotranscendens towards a more qualified humanity, which is in contact...

  17. Human gliomas contain morphine

    DEFF Research Database (Denmark)

    Olsen, Peter; Rasmussen, Mads; Zhu, Wei

    2005-01-01

    BACKGROUND: Morphine has been found in cancer cell lines originating from human and animal cells. Thus, it became important to demonstrate whether or not actual tumours contain this opiate alkaloid. MATERIAL/METHODS: Human glioma tissues were biochemically treated to isolate and separate endogeno...... of the solutions used in the study nor was it present as a residual material in blank HPLC runs. CONCLUSIONS: Morphine is present in human gliomas, suggesting that it may exert an action that effects tumour physiology/pathology.......BACKGROUND: Morphine has been found in cancer cell lines originating from human and animal cells. Thus, it became important to demonstrate whether or not actual tumours contain this opiate alkaloid. MATERIAL/METHODS: Human glioma tissues were biochemically treated to isolate and separate endogenous...

  18. The human cell atlas

    DEFF Research Database (Denmark)

    Regev, Aviv; Teichmann, Sarah A.; Lander, Eric S.

    2017-01-01

    The recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to identify all cell types in the human body. The Human Cell Atlas Project is an international...... collaborative effort that aims to define all human cell types in terms of distinctive molecular profiles (such as gene expression profiles) and to connect this information with classical cellular descriptions (such as location and morphology). An open comprehensive reference map of the molecular state of cells...... in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease. Here we describe the idea, its potential utility, early...

  19. UN human rights council

    Directory of Open Access Journals (Sweden)

    Vuksanović Mlrjana

    2014-01-01

    Full Text Available The paper deals with the structure, mechanisms, practices and perspectives of the Human Rights Council, the UN body that, at universal level is the most important body in this area. Introductory section provides for a brief overview of the origins of human rights and the work of the Commission on Human Rights, in whose jurisdiction were questions of human rights before the establishment of the Council. After the introductory section the author gives an analysis of the structure, objectives, mandate and main procedures for the protection of human rights within the united Nations. In the final section the authorpoints out the advantages of this authority and criticism addressed to it, with emphasis on the possibility and the need for its reform.

  20. Waste - the human factor

    International Nuclear Information System (INIS)

    McLaren, D.J.

    1993-01-01

    Waste is a human concept, referring to things that have no use to human beings and arising entirely from human activities. It is the useless residue of any human process that affects the economy or environment. The changes brought about by the industrial revolution are enormous; fossil fuels, not just photosynthesis, now provide energy and wastes at rates far exceeding the capacity of the ecosystem to absorb or recycle. Three major problems face the Planet: accelerated population growth, accelerated use of resources for energy and industry, and the disproportionate use of resources and waste between the northern and southern parts of the Planet. Knowledge and science are in a position to provide both human creativity and the directed technology to take remedial action and rediscover harmony between nature and mankind. Only social and political will is lacking

  1. Managing human performance

    International Nuclear Information System (INIS)

    Strucic, M.; Kavsek, D.

    2004-01-01

    Human performance remains a significant factor for management attention not only from a reactor safety perspective, but also from a financial one. Recent significant events analysis shows that human errors are still dominant causes and contributors to them. An analysis of significant events in nuclear industry occurred through 15-years period revealed that three of four significant events were triggered by human error, although the number of events have dropped by more than a factor of four. A number of human performance breakdowns occurred in the application of errorprevention techniques. These included a lack of pre-job briefs, inadequate turnover of tasks, ineffective use of peer checking, inadequate procedure adherence, and failure to apply a questioning attitude when unexpected changes were encountered in the task. Attempts by the industry to improve human performance have traditionally focused at the worker level. However, human error occurs within the context of the organization, which can either foster or resist human error. The greatest room for improvement lies not only in the continued improvement of front-line worker performance but more so in the identification and elimination of weaknesses in the organizational and managerial domains that contributes to worker performance at the job site. Based on mentioned analysis, other industrial sources and own operating experience, NPP Krsko is paying more attention to improve human performance among own as well as contractor workers. Through series of programs and activities, such as Reactivity Management Program, Safety Culture Program, Self-assessment Program, Corrective Action Program, Plant Performance Monitoring Program, developed in last few years, and through new procedures, written guides and publications, training and management efforts, number of human errors is going to be reduced. Involvement of higher levels of NPP Krsko organization in promotion and use of Human Performance techniques is

  2. Digital Human Modeling

    Science.gov (United States)

    Dischinger, H. Charles, Jr.

    2017-01-01

    The development of models to represent human characteristics and behaviors in human factors is broad and general. The term "model" can refer to any metaphor to represent any aspect of the human; it is generally used in research to mean a mathematical tool for the simulation (often in software, which makes the simulation digital) of some aspect of human performance and for the prediction of future outcomes. This section is restricted to the application of human models in physical design, e.g., in human factors engineering. This design effort is typically human interface design, and the digital models used are anthropometric. That is, they are visual models that are the physical shape of humans and that have the capabilities and constraints of humans of a selected population. They are distinct from the avatars used in the entertainment industry (movies, video games, and the like) in precisely that regard: as models, they are created through the application of data on humans, and they are used to predict human response; body stresses workspaces. DHM enable iterative evaluation of a large number of concepts and support rapid analysis, as compared with use of physical mockups. They can be used to evaluate feasibility of escape of a suited astronaut from a damaged vehicle, before launch or after an abort (England, et al., 2012). Throughout most of human spaceflight, little attention has been paid to worksite design for ground workers. As a result of repeated damage to the Space Shuttle which adversely affected flight safety, DHM analyses of ground assembly and maintenance have been developed over the last five years for the design of new flight systems (Stambolian, 2012, Dischinger and Dunn Jackson, 2014). The intent of these analyses is to assure the design supports the work of the ground crew personnel and thereby protect the launch vehicle. They help the analyst address basic human factors engineering questions: can a worker reach the task site from the work platform

  3. Human Milk Banking.

    Science.gov (United States)

    Haiden, Nadja; Ziegler, Ekhard E

    2016-01-01

    Human milk banks play an essential role by providing human milk to infants who would otherwise not be able to receive human milk. The largest group of recipients are premature infants who derive very substantial benefits from it. Human milk protects premature infants from necrotizing enterocolitis and from sepsis, two devastating medical conditions. Milk banks collect, screen, store, process, and distribute human milk. Donating women usually nurse their own infants and have a milk supply that exceeds their own infants' needs. Donor women are carefully selected and are screened for HIV-1, HIV-2, human T-cell leukemia virus 1 and 2, hepatitis B, hepatitis C, and syphilis. In the milk bank, handling, storing, processing, pooling, and bacterial screening follow standardized algorithms. Heat treatment of human milk diminishes anti-infective properties, cellular components, growth factors, and nutrients. However, the beneficial effects of donor milk remain significant and donor milk is still highly preferable in comparison to formula. © 2017 S. Karger AG, Basel.

  4. Human factors information system

    International Nuclear Information System (INIS)

    Goodman, P.C.; DiPalo, C.A.

    1991-01-01

    Nuclear power plant safety is dependent upon human performance related to plant operations. To provide improvements in human performance, data collection and assessment play key roles. This paper reports on the Human factors Information System (HFIS) which is designed to meet the needs of the human factors specialists of the United States Nuclear Regulatory Commission. These specialists identify personnel errors and provide guidance designed to prevent such errors. HFIS is a simple and modular system designed for use on a personal computer. It is designed to contain four separate modules that provide information indicative of program or function effectiveness as well as safety-related human performance based on programmatic and performance data. These modules include the Human Factors Status module; the Regulatory Programs module; the Licensee Event Report module; and the Operator Requalification Performance module. Information form these modules can either be used separately or can be combined due to the integrated nature of the system. HFIS has the capability, therefore, to provide insights into those areas of human factors that can reduce the probability of events caused by personnel error at nuclear power plants and promote the health and safety of the public. This information system concept can be applied to other industries as well as the nuclear industry

  5. Genetics of human hydrocephalus

    Science.gov (United States)

    Williams, Michael A.; Rigamonti, Daniele

    2006-01-01

    Human hydrocephalus is a common medical condition that is characterized by abnormalities in the flow or resorption of cerebrospinal fluid (CSF), resulting in ventricular dilatation. Human hydrocephalus can be classified into two clinical forms, congenital and acquired. Hydrocephalus is one of the complex and multifactorial neurological disorders. A growing body of evidence indicates that genetic factors play a major role in the pathogenesis of hydrocephalus. An understanding of the genetic components and mechanism of this complex disorder may offer us significant insights into the molecular etiology of impaired brain development and an accumulation of the cerebrospinal fluid in cerebral compartments during the pathogenesis of hydrocephalus. Genetic studies in animal models have started to open the way for understanding the underlying pathology of hydrocephalus. At least 43 mutants/loci linked to hereditary hydrocephalus have been identified in animal models and humans. Up to date, 9 genes associated with hydrocephalus have been identified in animal models. In contrast, only one such gene has been identified in humans. Most of known hydrocephalus gene products are the important cytokines, growth factors or related molecules in the cellular signal pathways during early brain development. The current molecular genetic evidence from animal models indicate that in the early development stage, impaired and abnormal brain development caused by abnormal cellular signaling and functioning, all these cellular and developmental events would eventually lead to the congenital hydrocephalus. Owing to our very primitive knowledge of the genetics and molecular pathogenesis of human hydrocephalus, it is difficult to evaluate whether data gained from animal models can be extrapolated to humans. Initiation of a large population genetics study in humans will certainly provide invaluable information about the molecular and cellular etiology and the developmental mechanisms of human

  6. Human Power Empirically Explored

    Energy Technology Data Exchange (ETDEWEB)

    Jansen, A.J.

    2011-01-18

    Harvesting energy from the users' muscular power to convert this into electricity is a relatively unknown way to power consumer products. It nevertheless offers surprising opportunities for product designers; human-powered products function independently from regular power infrastructure, are convenient and can be environmentally and economically beneficial. This work provides insight into the knowledge required to design human-powered energy systems in consumer products from a scientific perspective. It shows the developments of human-powered products from the first introduction of the BayGen Freeplay radio in 1995 till current products and provides an overview and analysis of 211 human-powered products currently on the market. Although human power is generally perceived as beneficial for the environment, this thesis shows that achieving environmental benefit is only feasible when the environmental impact of additional materials in the energy conversion system is well balanced with the energy demands of the products functionality. User testing with existing products showed a preference for speeds in the range of 70 to 190 rpm for crank lengths from 32 to 95 mm. The muscular input power varied from 5 to 21 W. The analysis of twenty graduation projects from the Faculty of Industrial Design Engineering in the field of human-powered products, offers an interesting set of additional practice based design recommendations. The knowledge based approach of human power is very powerful to support the design of human-powered products. There is substantial potential for improvements in the domains energy conversion, ergonomics and environment. This makes that human power, when applied properly, is environmentally and economically competitive over a wider range of applications than thought previously.

  7. Human dignity and bioethics

    Directory of Open Access Journals (Sweden)

    Marjanović Miloš

    2013-01-01

    Full Text Available By opening the field of bioethics followed a new wave of intense debate on the theological, philosophical and legal significance of the concept of human dignity . Exactly ten years ago (December 2003 American bioethicist Ruth Maclin has proposed to divest ourselves of the concept of human dignity because it is vague, useless and redundant and that, without any loss, we can replace it by the ethical principle of personal autonomy. Her article was followed by harsh reactions and opposite views. What is this term in so broad, almost inflationary and opposite use is not a reason to deprive him, but, on the contrary, it shows how important it is and that it should be determined at least outline. As universal values and general concept, the human dignity has no pre-defined and narrow, precise meaning. It is more an evaluation horizon, the guiding principle and regulatory ideas that must constantly define and codify by many guaranted human rights and fundamental freedoms. As generic notion of each reasonable law, it is their foundation and a common denominator, legitimising basis of natural but also of positive law. As intrinsic and static value which means the humaneness, the humanity it is absolute, inherent to every human being without distinction and conditioning, as a unique and unrepeatable creation. In this meaning, the dignity is the obligation and limitation of the state, society and each of us. As an ethical and dynamic category, it is not given to us, but it is assign to us, and it is not in us, but always before us, as a guide of our actions in accordance with virtues, to treat ourselves, each other and the nature in a human way. The century in which we live is named the century of molecular biology and genetic engineering because of the enormous potential but also risks to human dignity. Because of that human dignity has become a central principle in all international documents relating to the human genome, genetics and bioethics, adopted

  8. Human Genome Project

    Energy Technology Data Exchange (ETDEWEB)

    Block, S. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Cornwall, J. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Dally, W. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Dyson, F. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Fortson, N. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Joyce, G. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Kimble, H. J. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Lewis, N. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Max, C. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Prince, T. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Schwitters, R. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Weinberger, P. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Woodin, W. H. [The MITRE Corporation, McLean, VA (US). JASON Program Office

    1998-01-04

    The study reviews Department of Energy supported aspects of the United States Human Genome Project, the joint National Institutes of Health/Department of Energy program to characterize all human genetic material, to discover the set of human genes, and to render them accessible for further biological study. The study concentrates on issues of technology, quality assurance/control, and informatics relevant to current effort on the genome project and needs beyond it. Recommendations are presented on areas of the genome program that are of particular interest to and supported by the Department of Energy.

  9. Aluminium in human sweat.

    Science.gov (United States)

    Minshall, Clare; Nadal, Jodie; Exley, Christopher

    2014-01-01

    It is of burgeoning importance that the human body burden of aluminium is understood and is measured. There are surprisingly few data to describe human excretion of systemic aluminium and almost no reliable data which relate to aluminium in sweat. We have measured the aluminium content of sweat in 20 healthy volunteers following mild exercise. The concentration of aluminium ranged from 329 to 5329μg/L. These data equate to a daily excretion of between 234 and 7192μg aluminium and they strongly suggest that perspiration is the major route of excretion of systemic aluminium in humans. Copyright © 2013 Elsevier GmbH. All rights reserved.

  10. Human exposure to aluminium.

    Science.gov (United States)

    Exley, Christopher

    2013-10-01

    Human activities have circumvented the efficient geochemical cycling of aluminium within the lithosphere and therewith opened a door, which was previously only ajar, onto the biotic cycle to instigate and promote the accumulation of aluminium in biota and especially humans. Neither these relatively recent activities nor the entry of aluminium into the living cycle are showing any signs of abating and it is thus now imperative that we understand as fully as possible how humans are exposed to aluminium and the future consequences of a burgeoning exposure and body burden. The aluminium age is upon us and there is now an urgent need to understand how to live safely and effectively with aluminium.

  11. Avian and human metapneumovirus.

    Science.gov (United States)

    Broor, Shobha; Bharaj, Preeti

    2007-04-01

    Pneumovirus infection remains a significant problem for both human and veterinary medicine. Both avian pneumovirus (aMPV, Turkey rhinotracheitis virus) and human metapneumovirus (hMPV) are pathogens of birds and humans, which are associated with respiratory tract infections. Based on their different genomic organization and low level of nucleotide (nt) and amino acid (aa) identity with paramyxoviruses in the genus Pneumovirus, aMPV and hMPV have been classified into a new genus referred to as Metapneumovirus. The advancement of our understanding of pneumovirus biology and pathogenesis of pneumovirus disease in specific natural hosts can provide us with strategies for vaccine formulations and combined antiviral and immunomodulatory therapies.

  12. Refractoriness in human atria

    DEFF Research Database (Denmark)

    Skibsbye, Lasse; Jespersen, Thomas; Christ, Torsten

    2016-01-01

    BACKGROUND: Refractoriness of cardiac cells limits maximum frequency of electrical activity and protects the heart from tonic contractions. Short refractory periods support major arrhythmogenic substrates and augmentation of refractoriness is therefore seen as a main mechanism of antiarrhythmic...... drugs. Cardiomyocyte excitability depends on availability of sodium channels, which involves both time- and voltage-dependent recovery from inactivation. This study therefore aims to characterise how sodium channel inactivation affects refractoriness in human atria. METHODS AND RESULTS: Steady......-state activation and inactivation parameters of sodium channels measured in vitro in isolated human atrial cardiomyocytes were used to parameterise a mathematical human atrial cell model. Action potential data were acquired from human atrial trabeculae of patients in either sinus rhythm or chronic atrial...

  13. Human Reliability Program Overview

    Energy Technology Data Exchange (ETDEWEB)

    Bodin, Michael

    2012-09-25

    This presentation covers the high points of the Human Reliability Program, including certification/decertification, critical positions, due process, organizational structure, program components, personnel security, an overview of the US DOE reliability program, retirees and academia, and security program integration.

  14. Human Papillomavirus (HPV) Vaccines

    Science.gov (United States)

    ... factors for developing them, such as taking oral contraceptives . A safety review of Gardasil in Denmark and ... and venous thromboembolic adverse events after immunisation of adolescent girls with quadrivalent human papillomavirus vaccine in Denmark ...

  15. Human-Machine Communication

    International Nuclear Information System (INIS)

    Farbrot, J.E.; Nihlwing, Ch.; Svengren, H.

    2005-01-01

    New requirements for enhanced safety and design changes in process systems often leads to a step-wise installation of new information and control equipment in the control room of older nuclear power plants, where nowadays modern digital I and C solutions with screen-based human-machine interfaces (HMI) most often are introduced. Human factors (HF) expertise is then required to assist in specifying a unified, integrated HMI, where the entire integration of information is addressed to ensure an optimal and effective interplay between human (operators) and machine (process). Following a controlled design process is the best insurance for ending up with good solutions. This paper addresses the approach taken when introducing modern human-machine communication in the Oskarshamn 1 NPP, the results, and the lessons learned from this work with high operator involvement seen from an HF point of view. Examples of possibilities modern technology might offer for the operators are also addressed. (orig.)

  16. Human Bond Communication

    DEFF Research Database (Denmark)

    Prasad, Ramjee

    2016-01-01

    Modern dexterous communication technology is progressively enabling humans to communicate their information through them with speech (aural) and media (optical) as underpinning essence. Humans realize this kind of aural and optical information by their optical and auditory senses. However, due...... to certain constraints, the ability to incorporate the other three sensory features namely, olfactory, gustatory, and tactile are still far from reality. Human bond communication is a novel concept that incorporates olfactory, gustatory, and tactile that will allow more expressive and holistic sensory...... information exchange through communication techniques for more human sentiment centric communication. This concept endorses the need of inclusion of other three senses and proposes an innovative approach of holistic communication for future communication network....

  17. OAS :: Accountability :: Human Resources

    Science.gov (United States)

    OAS, including its organizational structure, each organizational unit's staffing, vacant posts, and a list of procurement notices for formal bids, links to the performance contract and travel control Plan Human Resources Organizational Structure Functions of each organizational unit Vacant Posts

  18. Spaceflight Versus Human Spaceflight

    Science.gov (United States)

    Barr, Stephanie

    2013-09-01

    Spaceflight is challenging. Human spaceflight is far more challenging,.Those familiar with spaceflight recognize that human spaceflight is more than tacking an environmental control system on an existing spacecraft, that there are a number of serious technical challenges involved in sending people out into space and bringing them back home safely.The return trip, bringing the crew back to the surface of the earth safely, is more than just an additional task, it's the new imperative. Differences between manned and unmanned spaceflight are more than technical. The human element forces a change in philosophy, a mindset that will likely touch every aspect of flight from launch through mission and return. Seasoned space professionals used to the paradigms and priorities of unmanned flight need to be cognizant of these differences and some of the implications, perhaps most especially because mission success and human safety priorities are sometimes contradictory.

  19. Calvin and human dignity

    Directory of Open Access Journals (Sweden)

    J.M. Vorster

    2010-07-01

    Full Text Available Human dignity has become a major moral directive in the contemporary ethical reflection on human rights and bio-ethics. This article examines the theological foundations laid by the reformer Calvin regarding the inherent dignity of people, and his influence on post-World War ethical reflection about the violations of human rights. In this article his views on the “imago dei” and common grace, the “lex naturae” and the obligations of the civil authority are investigated in order to illuminate his ideas about the dignity of human beings. The article then deals with the influence of these ideas in the influential works of the twentieth century’s reformed theologians Barth, Berkhouwer and Moltmann.

  20. Designing Human Technologies

    DEFF Research Database (Denmark)

    Simonsen, Jesper

    and the design process, in ethical and society-related concerns, and in evaluating how designs fulfill needs and solve problems. Designing Human Technologies subscribes to a broad technology concept including information and communication, mobile, environmental/sustainable and energy technologies......Design is increasingly becoming a part of the university curriculum and research agenda. The keynote present and discuss Designing Human Technologies – an initiative aiming at establishing a design oriented main subject area alongside traditional main subject areas such as Natural Science......, the Humanities, and Social Science. The initiative broadens the perspective of IS and recognize reflections on aesthetics, ethics, values, connections to politics, and strategies for enabling a better future as legitimate parts of the research agenda. Designing Human Technologies is a design-oriented Strategic...

  1. Visible Human Project

    Science.gov (United States)

    ... cryosections are associated with anatomical terminology. AnatLine : A prototype system consisting of an anatomical image database and ... further information is available Publications VHJOE: Visible Human Journal of Endoscopy. NLM's Current Bibliographies in Medicine, Visible ...

  2. BIOETHICS AND HUMAN CLONING

    Directory of Open Access Journals (Sweden)

    Željko Kaluđerović

    2011-12-01

    Full Text Available In this paper the authors analyze the process of negotiating and beginning of the United Nations Declaration on Human Cloning as well as the paragraphs of the very Declaration. The negotiation was originally conceived as a clear bioethical debate that should have led to a general agreement to ban human cloning. However, more often it had been discussed about human rights, cultural, civil and religious differences between people and about priorities in case of eventual conflicts between different value systems. In the end, a non-binding Declaration on Human Cloning had been adopted, full of numerous compromises and ambiguous formulations, that relativized the original intention of proposer states. According to authors, it would have been better if bioethical discussion and eventual regulations on cloning mentioned in the following text had been left over to certain professional bodies, and only after the public had been fully informed about it should relevant supranational organizations have taken that into consideration.

  3. Human Research Program

    Data.gov (United States)

    National Aeronautics and Space Administration — Strategically, the HRP conducts research and technology development that: 1) enables the development or modification of Agency-level human health and performance...

  4. Bridging Humanism and Behaviorism.

    Science.gov (United States)

    Chu, Lily

    1980-01-01

    Humanistic behaviorism may provide the necessary bridge between behaviorism and humanism. Perhaps the most humanistic approach to teaching is to learn how certain changes will help students and how these changes can be accomplished. (Author/MLF)

  5. Humanism vs. Behaviorism

    Science.gov (United States)

    Hunter, Madeline

    1977-01-01

    Author argues that humanism and behaviorism are not necessarily exclusive of one another, and that principles of behaviorism, when thoughtfully applied, can lead to the achievement of humanistic goals. (RW)

  6. Human factors in aviation

    National Research Council Canada - National Science Library

    Salas, Eduardo; Maurino, Daniel E

    2010-01-01

    .... HFA offers a comprehensive overview of the topic, taking readers from the general to the specific, first covering broad issues, then the more specific topics of pilot performance, human factors...

  7. Human Capital Tracking Tool -

    Data.gov (United States)

    Department of Transportation — AVS is now required to collect, track, and report on data from the following Flight, Business and Workforce Plan. The Human Resource Management’s Performance Target...

  8. Human Factors Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — Purpose: The purpose of the Human Factors Laboratory is to further the understanding of highway user needs so that those needs can be incorporated in roadway design,...

  9. Evaluating human genetic diversity

    National Research Council Canada - National Science Library

    ... into human evolution and origins and serving as a springboard for important medical research. It also addresses issues of confidentiality and individual privacy for participants in genetic diversity research studies.

  10. Biotechnology and human rights.

    Science.gov (United States)

    Feuillet-Le Mintier, B

    2001-12-01

    Biotechnology permits our world to progress. It's a tool to better apprehend the human being, but as well to let him go ahead. Applied to the living, biotechnologies present the same finality. But since their matter concerns effectively the living, they are the sources of specific dangers and particularly of that one to use the improvements obtained on the human to modify the human species. The right of the persons has to find its place to avoid that the fundamental rights of the human personality shall undergo harm. This mission assigned to the right of the persons is as so much invaluable that the economical stakes are particularly important in the domain of the biotechnologies.

  11. Human-Robot Teams Informed by Human Performance Moderator Functions

    Science.gov (United States)

    2012-08-29

    performance factors that affect the ability of a human to drive at night, which includes the eyesight of the driver, the fatigue level of the driver...where human factors are factors that affect the performance of an individual. 7 for human interaction. For instance, they explain the various human... affecting trust in human-robot interaction. Human Factors 53(5), 517-527 (2001) 35. Hart, S. G. and Staveland, L. E. Development of NASA-TLX (Task

  12. Human Assisted Assembly Processes

    Energy Technology Data Exchange (ETDEWEB)

    CALTON,TERRI L.; PETERS,RALPH R.

    2000-01-01

    Automatic assembly sequencing and visualization tools are valuable in determining the best assembly sequences, but without Human Factors and Figure Models (HFFMs) it is difficult to evaluate or visualize human interaction. In industry, accelerating technological advances and shorter market windows have forced companies to turn to an agile manufacturing paradigm. This trend has promoted computerized automation of product design and manufacturing processes, such as automated assembly planning. However, all automated assembly planning software tools assume that the individual components fly into their assembled configuration and generate what appear to be a perfectly valid operations, but in reality the operations cannot physically be carried out by a human. Similarly, human figure modeling algorithms may indicate that assembly operations are not feasible and consequently force design modifications; however, if they had the capability to quickly generate alternative assembly sequences, they might have identified a feasible solution. To solve this problem HFFMs must be integrated with automated assembly planning to allow engineers to verify that assembly operations are possible and to see ways to make the designs even better. Factories will very likely put humans and robots together in cooperative environments to meet the demands for customized products, for purposes including robotic and automated assembly. For robots to work harmoniously within an integrated environment with humans the robots must have cooperative operational skills. For example, in a human only environment, humans may tolerate collisions with one another if they did not cause much pain. This level of tolerance may or may not apply to robot-human environments. Humans expect that robots will be able to operate and navigate in their environments without collisions or interference. The ability to accomplish this is linked to the sensing capabilities available. Current work in the field of cooperative

  13. Pushing Human Frontiers

    Science.gov (United States)

    Zubrin, Robert

    2005-01-01

    With human colonization of Mars, I think you will see a higher standard of civilization, just as America set a higher standard of civilization which then promulgated back into Europe. I think that if you want to maximize human potential, you need a higher standard of civilization, and that becomes an example that benefits everyone. Without an open frontier, closed world ideologies, such as the Malthus Theory, tend to come to the forefront. It is that there are limited resources; therefore, we are all in deadly competition with each other for the limited pot. The result is tyrannical and potentially genocidal regimes, and we've already seen this in the twentieth century. There s no truth in the Malthus Theory, because human beings are the creators of their resources. With every mouth comes a pair of hands and a brain. But if it seems to be true, you have a vector in this direction, and it is extremely unfortunate. It is only in a universe of infinite resources that all humans can be brothers and sisters. The fundamental question which affects humanity s sense of itself is whether the world is changeable or fixed. Are we the makers of our world or just its inhabitants? Some people have a view that they re living at the end of history within a world that s already defined, and there is no fundamental purpose to human life because there is nothing humans can do that matters. On the other hand, if humans understand their own role as the creators of their world, that s a much more healthy point of view. It raises the dignity of humans. Indeed, if we do establish a new branch of human civilization on Mars that grows in time and potency to the point where it cannot really settle Mars, but transforms Mars, and brings life to Mars, we will prove to everyone and for all time the precious and positive nature of the human species and every member of it.

  14. Business and Human Rights

    DEFF Research Database (Denmark)

    Buhmann, Karin

    2015-01-01

    This article analyses the United Nations (UN) Guidelines on Business and Human Rights adopted in 2011 by the UN Human Rights Council from the perspective of transnational business governance interactions (TBGI) analytical framework.1 The article identifies and discusses dimensions of interaction...... in several areas of relevance to transnational business governance interaction and indicates the relevance of the TBGI approach to public regulatory transnational business governance initiatives. The analysis of the Guiding Principles as interactional transnational business governance suggests that this form...

  15. Quality and human society

    Science.gov (United States)

    Stoll, W.

    1991-02-01

    Quality of products and services is seen as a necessity in our modern world. Quality also has important cross-links to safety in our society. It is however suggested, that human beings are living in their industrial environment under the stress of a fractured personality with anxieties and frustrations. Some cultural comparisons with other industrial nations are given. Quality control tailored to human nature is recommended.

  16. Human ocular anatomy.

    Science.gov (United States)

    Kels, Barry D; Grzybowski, Andrzej; Grant-Kels, Jane M

    2015-01-01

    We review the normal anatomy of the human globe, eyelids, and lacrimal system. This contribution explores both the form and function of numerous anatomic features of the human ocular system, which are vital to a comprehensive understanding of the pathophysiology of many oculocutaneous diseases. The review concludes with a reference glossary of selective ophthalmologic terms that are relevant to a thorough understanding of many oculocutaneous disease processes. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Human Germline Genome Editing.

    Science.gov (United States)

    Ormond, Kelly E; Mortlock, Douglas P; Scholes, Derek T; Bombard, Yvonne; Brody, Lawrence C; Faucett, W Andrew; Garrison, Nanibaa' A; Hercher, Laura; Isasi, Rosario; Middleton, Anna; Musunuru, Kiran; Shriner, Daniel; Virani, Alice; Young, Caroline E

    2017-08-03

    With CRISPR/Cas9 and other genome-editing technologies, successful somatic and germline genome editing are becoming feasible. To respond, an American Society of Human Genetics (ASHG) workgroup developed this position statement, which was approved by the ASHG Board in March 2017. The workgroup included representatives from the UK Association of Genetic Nurses and Counsellors, Canadian Association of Genetic Counsellors, International Genetic Epidemiology Society, and US National Society of Genetic Counselors. These groups, as well as the American Society for Reproductive Medicine, Asia Pacific Society of Human Genetics, British Society for Genetic Medicine, Human Genetics Society of Australasia, Professional Society of Genetic Counselors in Asia, and Southern African Society for Human Genetics, endorsed the final statement. The statement includes the following positions. (1) At this time, given the nature and number of unanswered scientific, ethical, and policy questions, it is inappropriate to perform germline gene editing that culminates in human pregnancy. (2) Currently, there is no reason to prohibit in vitro germline genome editing on human embryos and gametes, with appropriate oversight and consent from donors, to facilitate research on the possible future clinical applications of gene editing. There should be no prohibition on making public funds available to support this research. (3) Future clinical application of human germline genome editing should not proceed unless, at a minimum, there is (a) a compelling medical rationale, (b) an evidence base that supports its clinical use, (c) an ethical justification, and (d) a transparent public process to solicit and incorporate stakeholder input. Copyright © 2017 American Society of Human Genetics. All rights reserved.

  18. Cytokines in human milk.

    Science.gov (United States)

    Garofalo, Roberto

    2010-02-01

    Epidemiologic studies conducted in the past 30 years to investigate the protective functions of human milk strongly support the notion that breastfeeding prevents infantile infections, particularly those affecting the gastrointestinal and respiratory tracts. However, more recent clinical and experimental observations also suggest that human milk not only provides passive protection, but also can directly modulate the immunological development of the recipient infant. The study of this remarkable defense system in human milk has been difficult because of its biochemical complexity, the small concentration of certain bioactive components, the compartmentalization of some of these agents, the dynamic quantitative and qualitative changes of milk during lactation, and the lack of specific reagents to quantify these agents. However, a host of bioactive substances, including hormones, growth factors, and immunological factors such as cytokines, have been identified in human milk. Cytokines are pluripotent polypeptides that act in autocrine/paracrine fashions by binding to specific cellular receptors. They operate in networks and orchestrate the development and functions of immune system. Several different cytokines and chemokines have been discovered in human milk in the past years, and the list is growing very rapidly. This article will review the current knowledge about the increasingly complex network of chemoattractants, activators, and anti-inflammatory cytokines present in human milk and their potential role in compensating for the developmental delay of the neonate immune system. Copyright 2010. Published by Mosby, Inc.

  19. Human Performance Evaluation System

    International Nuclear Information System (INIS)

    Hardwick, R.J. Jr.

    1985-01-01

    Operating nuclear power plants requires high standards of performance, extensive training and responsive management. Despite our best efforts inappropriate human actions do occur, but they can be managed. An extensive review of License Event Reports (LERs) was conducted which indicated continual inadequacy in human performance and in evaluation of root causes. Of some 31,000 LERs, about 5,000 or 16% were directly attributable to inappropriate actions. A recent analysis of 87 Significant Event Reports (issued by INPO in 1983) identified inappropriate actions as being the most frequent root cause (44% of the total). A more recent analysis of SERs issued in 1983 and 1984 indicate that 52% of the root causes were attributed to human performance. The Human Performance Evaluation System (HPES) is a comprehensive, coordinated utility/industry system for evaluating and reporting human performance situtations. HPES is a result of the realization that current reporting system provide limited treatment of human performance and rarely provide adequate information about root causes of inappropriate actions by individuals. The HPES was implemented to identify and eliminate root causes of inappropriate actions

  20. Human Factors Review Plan

    International Nuclear Information System (INIS)

    Paramore, B.; Peterson, L.R.

    1985-12-01

    ''Human Factors'' is concerned with the incorporation of human user considerations into a system in order to maximize human reliability and reduce errors. This Review Plan is intended to assist in the assessment of human factors conditions in existing DOE facilities. In addition to specifying assessment methodologies, the plan describes techniques for improving conditions which are found to not adequately support reliable human performance. The following topics are addressed: (1) selection of areas for review describes techniques for needs assessment to assist in selecting and prioritizing areas for review; (2) human factors engineering review is concerned with optimizing the interfaces between people and equipment and people and their work environment; (3) procedures review evaluates completeness and accuracy of procedures, as well as their usability and management; (4) organizational interface review is concerned with communication and coordination between all levels of an organization; and (5) training review evaluates training program criteria such as those involving: trainee selection, qualification of training staff, content and conduct of training, requalification training, and program management

  1. Human Factors Review Plan

    Energy Technology Data Exchange (ETDEWEB)

    Paramore, B.; Peterson, L.R. (eds.)

    1985-12-01

    ''Human Factors'' is concerned with the incorporation of human user considerations into a system in order to maximize human reliability and reduce errors. This Review Plan is intended to assist in the assessment of human factors conditions in existing DOE facilities. In addition to specifying assessment methodologies, the plan describes techniques for improving conditions which are found to not adequately support reliable human performance. The following topics are addressed: (1) selection of areas for review describes techniques for needs assessment to assist in selecting and prioritizing areas for review; (2) human factors engineering review is concerned with optimizing the interfaces between people and equipment and people and their work environment; (3) procedures review evaluates completeness and accuracy of procedures, as well as their usability and management; (4) organizational interface review is concerned with communication and coordination between all levels of an organization; and (5) training review evaluates training program criteria such as those involving: trainee selection, qualification of training staff, content and conduct of training, requalification training, and program management.

  2. A WORLD BEYOND HUMAN

    Directory of Open Access Journals (Sweden)

    David Abram

    2013-12-01

    Full Text Available From an initial project to investigate the relationship between magic and traditional medicine as practiced by shamans in Southern rural Asia, the focus of attention gradually shifted to an awareness of the negotiation traditional medicine people or shamans exert between the human community and the larger community of beings. This attentiveness to a more-than-human world does not occur at a supernatural domain above nature or inside her personal self but is the result of the shaman’s special ability to project her consciousness horizontally to other forms of sensibility with which human existence is interwoven. The ecological function of the shaman is to maintain a constant balance between what is taken and what is given from the human community to the larger community. The spirits of indigenous cultures are not defined in opposition to materiality but are essentially those modes of intelligence or awareness that do not possess a human form. By exploring different landscapes, and the sensibility living in them, a new sensitivity is awoken that allows for communication with those intelligences. However, the drowning of these other voices in Western culture, which reduces otherness to an object, creates an uneasiness that is hardly perceived except as an inability to interact with anything more-than-human and its dire consequences in the form of “civilization’s” destructive behavior.

  3. Deuteronomy and Human Rights

    Directory of Open Access Journals (Sweden)

    G. Braulik

    1998-08-01

    Full Text Available If one compares the articles of the "Universal Declaration of Human Rights" dated December 10th, 1948, with the regulations of the book of Deuteronomy, one detects a surprising abundance of correspondences, or at least of similar tendencies, between them. As the social theorists of the seventeenth and eighteenth centuries, the architects of the catalogue of Human Rights, knew the Scripture very well. References to Deuteronomy are historically well probable and factually hardly coincidental. Deuteronomy rightly boasts about its social laws (4:8 that are unique in the Ancient Near East. The paper orientates itself to the short formula of Human Rights and at the same time to the normative basic character of each human right, as it is formulated in the first article of the declaration: "liberty", "equality", "fraternity". Each of these basic categories are concretised in terms of several Deuteronomic regulations and prove themselves to be central matters of concern within the YHWH religion. Finally, it is outlined how the connection between Deuteronomy and modem expressions of human rights might be explained, and further it is shown what actually makes up the peculiarity of biblical thinking on human rights.

  4. Habitability and Human Factors Contributions to Human Space Flight

    Science.gov (United States)

    Sumaya, Jennifer Boyer

    2011-01-01

    This slide presentation reviews the work of the Habitability and Human Factors Branch in support of human space flight in two main areas: Applied support to major space programs, and Space research. The field of Human Factors applies knowledge of human characteristics for the design of safer, more effective, and more efficient systems. This work is in several areas of the human space program: (1) Human-System Integration (HSI), (2) Orion Crew Exploration Vehicle, (3) Extravehicular Activity (EVA), (4) Lunar Surface Systems, (5) International Space Station (ISS), and (6) Human Research Program (HRP). After detailing the work done in these areas, the facilities that are available for human factors work are shown.

  5. Human bites - self-care

    Science.gov (United States)

    Bites - human - self-care ... Human bites can occur in 2 ways: If someone bites you If your hand comes into contact ... bite to express anger or other negative feelings. Human bites may be more dangerous than animal bites. ...

  6. Tabhu: tools for antibody humanization.

    KAUST Repository

    Olimpieri, Pier Paolo; Marcatili, Paolo; Tramontano, Anna

    2014-01-01

    for antibody humanization. Tabhu includes tools for human template selection, grafting, back-mutation evaluation, antibody modelling and structural analysis, helping the user in all the critical steps of the humanization experiment protocol. AVAILABILITY: http

  7. Human dignity, humiliation, and torture.

    Science.gov (United States)

    Luban, David

    2009-09-01

    Modern human rights instruments ground human rights in the concept of human dignity, without providing an underlying theory of human dignity. This paper examines the central importance of human dignity, understood as not humiliating people, in traditional Jewish ethics. It employs this conception of human dignity to examine and criticize U.S. use of humiliation tactics and torture in the interrogation of terrorism suspects.

  8. Towards a better understanding of human smuggling

    OpenAIRE

    Heckmann, Friedrich

    2007-01-01

    Contents: What is human smuggling?; How can we know about human smuggling?; Human smuggling as a migration phenomenon; Human smuggling as a business; The social organizing of human smuggling; Fighting against human smuggling.

  9. Why Geo-Humanities

    Science.gov (United States)

    Graells, Robert Casals i.; Sibilla, Anna; Bohle, Martin

    2016-04-01

    Anthropogenic global change is a composite process. It consists of societal processes (in the 'noosphere') and natural processes (in the 'bio-geosphere'). The 'noosphere' is the ensemble of social, cultural or political insights ('shared subjective mental concepts') of people. Understanding the composite of societal and natural processes ('human geo-biosphere intersections'), which shapes the features of anthropogenic global change, would benefit from a description that draws equally on natural sciences, social sciences and humanities. To that end it is suggested to develop a concept of 'geo-humanities': This essay presents some aspects of its scope, discussing "knowledge that is to manage", "intentions that are to shape", "choices that are to justify" and "complexity that is to handle". Managing knowledge: That people understand anthropogenic global change requires their insights into how 'human geosphere intersections' function. Insights are formed ('processed') in the noosphere by means of interactions between people. Understanding how 'human geosphere intersections' functions combines scientific, engineering and economic studies with studies of the dynamics of the noosphere. Shaping intentions: During the last century anthropogenic global change developed as the collateral outcome of humankind's accumulated actions. It is caused by the number of people, the patterns of their consumption of resources, and the alterations of their environments. Nowadays, anthropogenic global chance is either an intentional negligence or a conscious act. Justifying choices: Humanity has alternatives how to alter Earth at planetary scale consciously. For example, there is a choice to alter the geo-biosphere or to adjust the noosphere. Whatever the choice, it will depend on people's world-views, cultures and preferences. Thus beyond issues whether science and technology are 'sound' overarching societal issues are to tackle, such as: (i) how to appropriate and distribute natural

  10. The Human Serum Metabolome

    Science.gov (United States)

    Psychogios, Nikolaos; Hau, David D.; Peng, Jun; Guo, An Chi; Mandal, Rupasri; Bouatra, Souhaila; Sinelnikov, Igor; Krishnamurthy, Ramanarayan; Eisner, Roman; Gautam, Bijaya; Young, Nelson; Xia, Jianguo; Knox, Craig; Dong, Edison; Huang, Paul; Hollander, Zsuzsanna; Pedersen, Theresa L.; Smith, Steven R.; Bamforth, Fiona; Greiner, Russ; McManus, Bruce; Newman, John W.; Goodfriend, Theodore; Wishart, David S.

    2011-01-01

    Continuing improvements in analytical technology along with an increased interest in performing comprehensive, quantitative metabolic profiling, is leading to increased interest pressures within the metabolomics community to develop centralized metabolite reference resources for certain clinically important biofluids, such as cerebrospinal fluid, urine and blood. As part of an ongoing effort to systematically characterize the human metabolome through the Human Metabolome Project, we have undertaken the task of characterizing the human serum metabolome. In doing so, we have combined targeted and non-targeted NMR, GC-MS and LC-MS methods with computer-aided literature mining to identify and quantify a comprehensive, if not absolutely complete, set of metabolites commonly detected and quantified (with today's technology) in the human serum metabolome. Our use of multiple metabolomics platforms and technologies allowed us to substantially enhance the level of metabolome coverage while critically assessing the relative strengths and weaknesses of these platforms or technologies. Tables containing the complete set of 4229 confirmed and highly probable human serum compounds, their concentrations, related literature references and links to their known disease associations are freely available at http://www.serummetabolome.ca. PMID:21359215

  11. Human Performance Event Database

    International Nuclear Information System (INIS)

    Trager, E. A.

    1998-01-01

    The purpose of this paper is to describe several aspects of a Human Performance Event Database (HPED) that is being developed by the Nuclear Regulatory Commission. These include the background, the database structure and basis for the structure, the process for coding and entering event records, the results of preliminary analyses of information in the database, and plans for the future. In 1992, the Office for Analysis and Evaluation of Operational Data (AEOD) within the NRC decided to develop a database for information on human performance during operating events. The database was needed to help classify and categorize the information to help feedback operating experience information to licensees and others. An NRC interoffice working group prepared a list of human performance information that should be reported for events and the list was based on the Human Performance Investigation Process (HPIP) that had been developed by the NRC as an aid in investigating events. The structure of the HPED was based on that list. The HPED currently includes data on events described in augmented inspection team (AIT) and incident investigation team (IIT) reports from 1990 through 1996, AEOD human performance studies from 1990 through 1993, recent NRR special team inspections, and licensee event reports (LERs) that were prepared for the events. (author)

  12. Humanity and Sustainability

    Directory of Open Access Journals (Sweden)

    Shu-Kun Lin

    2011-09-01

    Full Text Available So far our open access publishing company MDPI (Multidisciplinary Digital Publishing Institute has published mainly science, medicine and technology journals. To become a multidisciplinary publisher, we launched the journal Sustainability [1]. More recently, we started to run several social science journals, including Societies [2], Religions [3], Administrative Sciences [4] and Behavioral Sciences [5]. Today we published the first paper [6] of the inaugural issue of Humanities (ISSN 2076-0787. This will be an international open access journal, publishing scholarly papers of high quality across all humanities disciplines. As a publisher, I would like to publish journals surrounding the topics of sustainability and I believe the humanities as a discipline of academic studies are very important. As a scientist, I believed science and technology will only benefit human beings. I was raised in a small village, living a very primitive life in a peasant family: no electricity, no machines, of course no TV and no refrigerator. Now, the life of my children is completely different. Even my own life has completely changed. I have witnessed very rapid changes: more and more machines are used to consume mineral resources and energy and to pollute the environment, in order to produce more and more powerful machines (we are also launching a journal titled Machines, in which the relationship between Man and machine should be an interesting topic.. Machines are more and more like human individuals consuming resources themselves (we are launching a journal titled Resources. [...

  13. Healthy human gut phageome.

    Science.gov (United States)

    Manrique, Pilar; Bolduc, Benjamin; Walk, Seth T; van der Oost, John; de Vos, Willem M; Young, Mark J

    2016-09-13

    The role of bacteriophages in influencing the structure and function of the healthy human gut microbiome is unknown. With few exceptions, previous studies have found a high level of heterogeneity in bacteriophages from healthy individuals. To better estimate and identify the shared phageome of humans, we analyzed a deep DNA sequence dataset of active bacteriophages and available metagenomic datasets of the gut bacteriophage community from healthy individuals. We found 23 shared bacteriophages in more than one-half of 64 healthy individuals from around the world. These shared bacteriophages were found in a significantly smaller percentage of individuals with gastrointestinal/irritable bowel disease. A network analysis identified 44 bacteriophage groups of which 9 (20%) were shared in more than one-half of all 64 individuals. These results provide strong evidence of a healthy gut phageome (HGP) in humans. The bacteriophage community in the human gut is a mixture of three classes: a set of core bacteriophages shared among more than one-half of all people, a common set of bacteriophages found in 20-50% of individuals, and a set of bacteriophages that are either rarely shared or unique to a person. We propose that the core and common bacteriophage communities are globally distributed and comprise the HGP, which plays an important role in maintaining gut microbiome structure/function and thereby contributes significantly to human health.

  14. Human hybrid hybridoma

    Energy Technology Data Exchange (ETDEWEB)

    Tiebout, R.F.; van Boxtel-Oosterhof, F.; Stricker, E.A.M.; Zeijlemaker, W.P.

    1987-11-15

    Hybrid hybridomas are obtained by fusion of two cells, each producing its own antibody. Several authors have reported the construction of murine hybrid hybridomas with the aim to obtain bispecific monoclonal antibodies. The authors have investigated, in a model system, the feasibility of constructing a human hybrid hybridoma. They fused two monoclonal cell lines: an ouabain-sensitive and azaserine/hypoxanthine-resistant Epstein-Barr virus-transformed human cell line that produces an IgG1kappa antibody directed against tetanus toxiod and an azaserine/hypoxanthine-sensitive and ouabain-resistant human-mouse xenohybrid cell line that produces a human IgG1lambda antibody directed against hepatitis-B surface antigen. Hybrid hybridoma cells were selected in culture medium containing azaserine/hypoxanthine and ouabain. The hybrid nature of the secreted antibodies was analyzed by means of two antigen-specific immunoassay. The results show that it is possible, with the combined use of transformation and xenohybridization techniques, to construct human hybrid hybridomas that produce bispecific antibodies. Bispecific antibodies activity was measured by means of two radioimmunoassays.

  15. Current treatments in Parkinson's including the proposal of an innovative dopamine microimplant

    Directory of Open Access Journals (Sweden)

    M. Velázquez-Paniagua

    2016-04-01

    Full Text Available Parkinson's disease is a chronic, debilitating, progressive neurological disorder of multifactorial origin. It affects between 0.3% and 2% of the over-65 population worldwide, with a predilection for men, and is characterised by bradykinesia, muscular rigidity, resting tremor and postural instability. Parkinson's is caused by decreased dopamine levels due to the loss of dopaminergic neurons in the substantia nigra. Because dopamine is a highly oxidisable molecule, precursors such as levodopa, together with catechol-O-methyltransferase and monoamine oxidase inhibitors to prevent degradation, are used in the treatment of this disease. These therapies, however, are not without their adverse effects. Surgical treatments for Parkinson's include pallidotomy, therapy deep brain stimulation, and stem cells. A more recent development involves a titanium dioxide micro-implant containing nanopores that stabilise the dopamine for continuous release. When inserted into the caudate nucleus, this micro-implant was found to counteract 85% of symptoms in hemiparkinsonian rats, and is a promising therapy for patients with Parkinson's disease.

  16. Dopamine Gene Profiling to Predict Impulse Control and Effects of Dopamine Agonist Ropinirole.

    Science.gov (United States)

    MacDonald, Hayley J; Stinear, Cathy M; Ren, April; Coxon, James P; Kao, Justin; Macdonald, Lorraine; Snow, Barry; Cramer, Steven C; Byblow, Winston D

    2016-07-01

    Dopamine agonists can impair inhibitory control and cause impulse control disorders for those with Parkinson disease (PD), although mechanistically this is not well understood. In this study, we hypothesized that the extent of such drug effects on impulse control is related to specific dopamine gene polymorphisms. This double-blind, placebo-controlled study aimed to examine the effect of single doses of 0.5 and 1.0 mg of the dopamine agonist ropinirole on impulse control in healthy adults of typical age for PD onset. Impulse control was measured by stop signal RT on a response inhibition task and by an index of impulsive decision-making on the Balloon Analogue Risk Task. A dopamine genetic risk score quantified basal dopamine neurotransmission from the influence of five genes: catechol-O-methyltransferase, dopamine transporter, and those encoding receptors D1, D2, and D3. With placebo, impulse control was better for the high versus low genetic risk score groups. Ropinirole modulated impulse control in a manner dependent on genetic risk score. For the lower score group, both doses improved response inhibition (decreased stop signal RT) whereas the lower dose reduced impulsiveness in decision-making. Conversely, the higher score group showed a trend for worsened response inhibition on the lower dose whereas both doses increased impulsiveness in decision-making. The implications of the present findings are that genotyping can be used to predict impulse control and whether it will improve or worsen with the administration of dopamine agonists.

  17. Pharmacotherapy for Parkinson's disease.

    Science.gov (United States)

    Chen, Jack J; Swope, David M

    2007-12-01

    The available pharmacotherapies for Parkinson's disease address symptomatology because no agent has been demonstrated to provide definite neuroprotection against the disease. Choice of pharmacotherapy must include consideration of short-term benefits as well as long-term consequences. Patients with mild Parkinson's disease often function adequately without symptomatic treatment. However, recent data suggest that initiation of treatment with a well-tolerated agent (e.g., the monoamine oxidase [MAO]-B inhibitor rasagiline) in the absence of functional impairment is associated with improved long-term outcomes. Consideration should also be given to many patient-specific factors, including patient expectations, level of disability, employment status, functional as well as chronologic age, expected efficacy and tolerability of drugs, and response to previous Parkinson's disease therapies. Increasingly, initial monotherapy begins with a nondopaminergic agent or, if the patient is considered functionally young, a dopamine agonist. Since Parkinson's disease is a progressive disorder, adjustments to pharmacotherapy must be expected over time. When greater symptomatic relief is desired, or in the more frail elderly patient, levodopa therapy should be considered. If motor fluctuations develop, addition of a catechol-O-methyltransferase inhibitor or MAO-B inhibitor should be considered. For management of levodopa-induced dyskinesias, addition of amantadine is an option. Surgery may be considered when patients need additional symptomatic control or are experiencing severe motor complications despite pharmacologically optimized therapy.

  18. Effects of divorce on Dutch boys' and girls' externalizing behavior in Gene × Environment perspective: diathesis stress or differential susceptibility in the Dutch Tracking Adolescents' Individual Lives Survey study?

    Science.gov (United States)

    Nederhof, Esther; Belsky, Jay; Ormel, Johan; Oldehinkel, Albertine J

    2012-08-01

    The effects of divorce on children's behavioral development have proven to be quite varied across studies, and most developmental and family scholars today appreciate the great heterogeneity in divorce effects. Thus, this inquiry sought to determine whether select dopaminergic genes previously associated with externalizing behavior and/or found to moderate diverse environmental effects (dopamine receptors D2 and D4, catechol-O-methyltransferase) might moderate divorce effects on adolescent self-reported externalizing problems; and, if so, whether evidence of gene-environment (G × E) interaction would prove consistent with diathesis-stress or differential-susceptibility models of environmental action. Data from the first and third wave of the Dutch Tracking Adolescents' Individual Lives Survey (n = 1,134) revealed some evidence of G × E interaction reflecting diathesis-stress but not differential susceptibility. It is intriguing that some evidence pointed to "vantage sensitivity," which are benefits accruing to those with a specific genotype when their parents remained together, the exact opposite of diathesis-stress. The limits of this work are considered, especially with regard to the conditions for testing differential susceptibility, and future directions are outlined.

  19. Molecular approaches to child psychopathology.

    Science.gov (United States)

    Alsobrook, J P; Pauls, D L

    1998-04-01

    Basic research into the genetics of childhood psychiatric disorders has substantially increased during the last two decades. Specific genetic mutations have been characterized in some developmental disorders (e.g., fragile X syndrome and Prader-Willi syndrome), but thus far identification of etiological gene mutations in psychiatric illnesses has been unsuccessful. Several psychiatric disorders serve as examples of the current state of molecular approaches in child psychopathology. Investigations to date of Gilles de la Tourette's syndrome (GTS) have not resulted in the discovery of a gene of major effect. Some studies have implicated the D2 and D4 dopamine receptors as having a direct role in the etiology of GTS, but other studies have disputed those findings. However, the dopamine D2 receptor may modulate the severity of GTS. Obsessive-compulsive disorder has a reported association with a low-activity allele of the enzyme catechol-O-methyltransferase; however, the low-activity genotype is also seen in a significant proportion of unaffected individuals. For reading disability two distinct phenotypes (phonological awareness and single-word reading) have been linked to separate loci on chromosomes 6 and 15. Attention deficit hyperactivity disorder (ADHD) has a reported association with the dopamine transporter. Findings of a genetic locus for the personality trait of novelty seeking remain controversial.

  20. Radioenzymatic assay of DOPA (3,4-dihydroxyphenylalanine)

    International Nuclear Information System (INIS)

    Johnson, G.A.; Gren, J.M.; Kupiecki, R.

    1978-01-01

    We modified the single-isotope radioenzymatic assay for catecholamines [Life Sci. 21, 625(1977)] to assay 3,4-dihydroxyphenylalanine (DOPA). DOPA decarboxylase is used to convert DOPA to dopamine, which concurrently is converted to [ 3 H]-3-O-methyldopamine in the presence of catechol-O-methyltransferase and [methyl- 3 H]-S-adenosylmethionine and assayed radioenzymatically. For assay of plasma DOPA, 50 μl of untreated plasma is added directly into the incubation mixture. A duplicate mixture containing an internal standard requires a second 50-μl aliquot of plasma. Because the assay measures both DOPA and endogenous dopamine, two additional aliquots of plasma must be assayed for dopamine in the absence of the decarboxylase by the differential assay; DOPA is estimated by difference. The assay is sensitive to 25 pg (500 ng/liter of plasma). Analysis of DOPA (DOPA plus dopamine) and the concurrent differential assay of catecholamines in at least 10 samples can be done in a single working day. Plasma DOPA concentrations for 42 normotensive adults were 1430 +- 19 ng/liter (mean +- SEM). In contrast, dopamine concentrations for these same subjects averaged 23 +- 20 ng/liter. Values for the 24 women subjects (1510 +- 62 ng/liter) significantly (P = 0.04) exceeded those for the men