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COMT met/met

Insiyyah Y Patanwala, Georgine Lamvu, William J Ledger, Kathryn Witzeman, Richard Marvel, Andrea Rapkin, Ann Marie Bongiovanni, Jessica Feranec, Steven S Witkin
BACKGROUND: The underlying causes of vulvar pain in women with vulvodynia remain poorly understood. Catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines, is a neuromodulator involved with perception and sensitivity to pain. The COMT gene is polymorphic and a single nucleotide polymorphism (SNP) is associated with low activity and heightened pain sensitivity. The variant allele encoding this polymorphism is commonly called the L allele, for low enzyme activity as opposed to the normal H (high activity) allele...
October 22, 2016: American Journal of Obstetrics and Gynecology
Ethan A Winkler, John K Yue, Adam R Ferguson, Nancy R Temkin, Murray B Stein, Jason Barber, Esther L Yuh, Sourabh Sharma, Gabriela G Satris, Thomas W McAllister, Jonathan Rosand, Marco D Sorani, Hester F Lingsma, Phiroz E Tarapore, Esteban G Burchard, Donglei Hu, Celeste Eng, Kevin K W Wang, Pratik Mukherjee, David O Okonkwo, Ramon Diaz-Arrastia, Geoffrey T Manley
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...
October 18, 2016: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
Rosario Montirosso, Livio Provenzi, Daniela Tavian, Sara Missaglia, Maria Elisabetta Raggi, Renato Borgatti
Individual variability exists in infants' socio-emotional stress regulation, in terms of behavioral response (i.e., negative emotionality) as well as magnitude and direction (i.e., increase or decrease) of hypothalamic-pituitary-adrenal (HPA) axis reactivity (i.e., salivary cortisol post-stress concentration). The catechol-O-methyltransferase polymorphism at codon 158 (COMTval158met) associates with stress regulation, but no evidence exists for infants. This study aimed to assess the association between COMTval158met and both negative emotionality and salivary cortisol reactivity to socio-emotional stress in 4-month-old infants...
October 12, 2016: Infant Behavior & Development
Christian Lerner, Roland Jakob-Roetne, Bernd Buettelmann, Andreas Ehler, Markus Rudolph, Rosa María Rodríguez Sarmiento
A fragment screening approach designed to target specifically the S-adenosyl-l-methionine pocket of catechol O-methyl transferase allowed the identification of structurally related fragments of high ligand efficiency and with activity on the described orthogonal assays. By use of a reliable enzymatic assay together with X-ray crystallography as guidance, a series of fragment modifications revealed an SAR and, after several expansions, potent lead compounds could be obtained. For the first time nonphenolic and small low nanomolar potent, SAM competitive COMT inhibitors are reported...
October 14, 2016: Journal of Medicinal Chemistry
Sanne J H van Rooij, Jennifer S Stevens, Timothy D Ely, Negar Fani, Alicia K Smith, Kimberly A Kerley, Adriana Lori, Kerry J Ressler, Tanja Jovanovic
Both childhood trauma and a functional catechol-O-methyltransferase (COMT) genetic polymorphism have been associated with posttraumatic stress disorder (PTSD) and depression; however, it is still unclear whether the two interact and how this interaction relates to long-term risk or resilience. Imaging and genotype data were collected on 73 highly traumatized women. DNA extracted from saliva was used to determine COMT genotype (Val/Val, n = 38, Met carriers, n = 35). Functional MRI data were collected during a Go/NoGo task to investigate the neurocircuitry underlying response inhibition...
2016: Frontiers in Psychiatry
Jiayuan Xu, Wen Qin, Qiaojun Li, Wei Li, Feng Liu, Bing Liu, Tianzi Jiang, Chunshui Yu
There exist gender differences in the modulation of catechol-O-methyltransferase (COMT) Val158Met polymorphism on cognitive performance; however, the underlying gene-anatomy-cognition pathways remain unknown. Here we hypothesize that prefrontal volume may mediate the modulation of COMT Val158Met polymorphism on interference resolution capacity in a gender-dependent manner. In 261 healthy young human subjects (143 males and 118 females), a 2-way analysis of variance showed a COMT × gender interaction (P = 0...
September 24, 2016: Cerebral Cortex
C L Clelland, V Drouet, K C Rilett, J A Smeed, R H Nadrich, A Rajparia, L L Read, J D Clelland
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...
2016: Translational Psychiatry
Colleen P Franconi, Donna McDonald-McGinn, Elaine H Zackai, Meghan A McNamara, Harold Salmons, Edward Moss, Raquel E Gur, Marcella Devoto, Beverly S Emanuel
22q11.2 Deletion Syndrome (22q11DS) is a multisystem disorder caused by a hemizygous deletion within 22q11.2. Patients with the deletion display a wide range of cognitive deficits. The gene catechol-O-methyl-transferase (COMT) resides in the typically deleted region of 22q11.2 and is rendered hemizygous in individuals affected by the 22q11DS. COMT is a critical enzyme in the degradation of catecholamine neurotransmitters in the brain. A functional polymorphism, Val(158) Met, has been associated with a variety of neurocognitive outcomes...
September 13, 2016: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Bei Wang, Wenzhao Ru, Xing Yang, Lu Yang, Pengpeng Fang, Xu Zhu, Guomin Shen, Xiaocai Gao, Pingyuan Gong
Dopamine levels in the brain influence human consciousness. Inspired by the role of Catechol-O-methyltransferase (COMT) in inactivating dopamine in the brain, we investigated to what extent COMT could modulate individual's self-consciousness dispositions and self-consistency by genotyping the COMT Val158Met (rs4680) polymorphism and measuring self-consciousness and self-consistency and congruence in a college student population. The results indicated that COMT Val158Met polymorphism significantly modulated the private self-consciousness...
August 2016: Consciousness and Cognition
Zhi Li, Beate W Hygen, Keith F Widaman, Turid S Berg-Nielsen, Lars Wichstrøm, Jay Belsky
Why is disorganized attachment associated with punitive-controlling behavior in some, but caregiving-controlling in others? Hygen et al. (2014) proposed that variation in the Catechol-O-methyl transferase(COMT) Val158Met genotype explains this variation, providing preliminary data to this effect. We offer a conceptual replication, analyzing data on 560 children (males: 275) drawn from the NICHD Study of Early Child Care and Youth Development. As predicted, competitive model-fitting indicated that disorganized infants carrying Met alleles engage in more positive behavior and less negative behavior than other children at age 5 and 11, with the reverse true of Val/Val homozygotes, seemingly consistent with caregiving-controlling and punitive-controlling styles, respectively, but only in the case of maternal and not teacher reports, thereby confirmating a relationship-specific hypothesis...
2016: Frontiers in Psychology
Danielle de Souza Costa, Jonas J de Paula, Antonio M Alvim-Soares, Patrícia A Pereira, Leandro F Malloy-Diniz, Luiz O C Rodrigues, Marco A Romano-Silva, Débora M de Miranda
Neurofibromatosis type I (NF1) is a neurogenetic disease marked by multiple cognitive and learning problems. Genetic variants may account for phenotypic variance in NF1. Here, we investigated the association between the catechol-O-methyltransferase (COMT) Val(158)Met polymorphism and working memory and arithmetic performance in 50 NF1 individuals. A significant association of the COMT polymorphism was observed only with verbal working memory, as measured by the backward digit-span task with an advantageous performance for Met/Met carriers...
2016: Frontiers in Human Neuroscience
Marco Bortolato, Consuelo Walss-Bass, Peter M Thompson, Jackob Moskovitz
OBJECTIVES: The enzyme catechol-O-methyltransferase (COMT), which catalyses the degradation of dopamine and norepinephrine, is posited to participate in the pathophysiology of bipolar disorder (BD) and schizophrenia. In support of this notion, rich evidence has documented that the severity of various BD and schizophrenia symptoms is moderated by rs4680, a single nucleotide polymorphism of the COMT gene featuring a valine (Val)-to-methionine (Met) substitution that results in lower catalytic activity...
July 26, 2016: World Journal of Biological Psychiatry
Yvette N Lamb, Nicole S McKay, Shrimal S Singh, Karen E Waldie, Ian J Kirk
The catechol-O-methyltransferase (COMT) val158met polymorphism affects the breakdown of synaptic dopamine. Consequently, this polymorphism has been associated with a variety of neurophysiological and behavioral outcomes. Some of the effects have been found to be sex-specific and it appears estrogen may act to down-regulate the activity of the COMT enzyme. The dopaminergic system has been implicated in face recognition, a form of cognition for which a female advantage has typically been reported. This study aimed to investigate potential joint effects of sex and COMT genotype on face recognition...
2016: Frontiers in Psychology
Esther D A van Duin, Liesbet Goossens, Dennis Hernaus, Fabiana da Silva Alves, Nicole Schmitz, Koen Schruers, Therese van Amelsvoort
BACKGROUND: 22q11.2 deletion syndrome (22q11DS) is caused by a microdeletion on chromosome 22q11.2 and associated with an increased risk to develop psychosis. The gene coding for catechol-O-methyl-transferase (COMT) is located at the deleted region, resulting in disrupted dopaminergic neurotransmission in 22q11DS, which may contribute to the increased vulnerability for psychosis. A dysfunctional motivational reward system is considered one of the salient features in psychosis and thought to be related to abnormal dopaminergic neurotransmission...
2016: Journal of Neurodevelopmental Disorders
Angélica Salatino-Oliveira, Joseph Murray, Christian Kieling, Júlia Pasqualini Genro, Guilherme Polanczyk, Luciana Anselmi, Fernando Wehrmeister, Fernando C de Barros, Ana Maria Baptista Menezes, Luis Augusto Rohde, Mara Helena Hutz
Conduct problems in childhood and adolescence are significant precursors of crime and violence in young adulthood. The purpose of the current study is to test the interaction between prenatal maternal smoking and COMT Val(158)Met in conduct problems and crime in the 1993 Pelotas Birth Cohort Study. Conduct problems were assessed through the parent version of the Strengths and Difficulties Questionnaire at ages 11 and 15 years. A translated version of a confidential self-report questionnaire was used to collect criminal data at 18 years of age...
2016: Scientific Reports
Pilar Lopez-Garcia, Alexandra Cristobal-Huerta, Leslie Young Espinoza, Patricio Molero, Felipe Ortuño Sanchez-Pedreño, Juan Antonio Hernández-Tamames
UNLABELLED: Context processing deficits have been shown to be present in chronic and first episode schizophrenia patients and in their relatives. This cognitive process is linked to frontal functioning and is highly dependent on dopamine levels in the prefrontal cortex (PFC). The catechol-O-methyltransferase (COMT) enzyme plays a prominent role in regulating dopamine levels in PFC. Genotypic variations in the functional polymorphism Val(158)Met COMT appear to have an impact in dopamine signaling in the PFC of healthy subjects and schizophrenia patients...
November 3, 2016: Progress in Neuro-psychopharmacology & Biological Psychiatry
C Barkus, C Korn, K Stumpenhorst, L M Laatikainen, D Ballard, S Lee, T Sharp, P J Harrison, D M Bannerman, D R Weinberger, J Chen, E M Tunbridge
Catechol-O-methyltransferase (COMT) modulates dopamine levels in the prefrontal cortex (PFC). The human gene contains a polymorphism (Val(158)Met) that alters enzyme activity and influences PFC function. It has also been linked with cognition and anxiety, but findings are mixed. We therefore developed a novel mouse model of altered COMT activity. The human Met allele was introduced into the native mouse COMT gene to produce COMT-Met mice, which were compared to their wild-type littermates. The model proved highly-specific: COMT-Met mice had reductions in COMT abundance and activity, compared with wild-types, explicitly in the absence of off-target changes in the expression of other genes...
July 8, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Jianyu Zhang, Judith P Klinman
Although an enormous and still growing number of biologically diverse methyltransferases have been reported and identified, a comprehensive understanding of the enzymatic methyl transfer mechanism is still lacking. Glycine N-methyltransferase (GNMT), a member of the family that acts on small metabolites as the substrate, catalyzes methyl transfer from S-adenosyl-l-methionine (AdoMet) to glycine to form S-adenosyl-l-homocysteine and sarcosine. We report primary carbon ((12)C/(14)C) and secondary ((1)H3/(3)H3) kinetic isotope effects at the transferred methyl group, together with (1)H3/(3)H3 binding isotope effects for wild-type GNMT and a series of Tyr21 mutants...
July 27, 2016: Journal of the American Chemical Society
Rajesh Narendran, Divya Tumuluru, Maureen A May, Kodavali V Chowdari, Michael L Himes, Kelli Fasenmyer, W Gordon Frankle, Vishwajit L Nimgaonkar
Basic investigations link a Val158Met polymorphism (rs4680) in the catechol-O-methyltransferase (COMT) gene to not only its enzymatic activity, but also to its dopaminergic tone in the prefrontal cortex. Previous PET studies have documented the relationship between COMT Val158Met polymorphism and D1 and D2/3 receptor binding potential (BP), and interpreted them in terms of dopaminergic tone. The use of baseline dopamine D1 and D2/3 receptor binding potential (BPND) as a proxy for dopaminergic tone is problematic because they reflect both endogenous dopamine levels (a change in radiotracer's apparent affinity) and receptor density...
2016: PloS One
Qiao Mao, Yun-Long Tan, Xing-Guang Luo, Li Tian, Zhi-Ren Wang, Shu-Ping Tan, Song Chen, Gui-Gang Yang, Hui-Mei An, Fu-De Yang, Xiang-Yang Zhang
Catechol-O-methyltransferase (COMT), an enzyme involved in the degradation and inactivation of the neurotransmitter dopamine, is associated with the sensory gating phenomenon, protecting the cerebral cortex from information overload. The COMT Val(108/158)Met polymorphism is essential for prefrontal cortex processing capacity and efficiency. The current study was designed to investigate the role of COMT Val(108/158)Met polymorphism in development, sensory gating deficit, and symptoms of schizophrenia in Han Chinese population...
August 30, 2016: Psychiatry Research
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