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catechol-o-methyltransferase and schizophrenia

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https://www.readbyqxmd.com/read/28273278/catechol-o-methyltransferase-comt-polymorphisms-modulate-working-memory-in-individuals-with-schizophrenia-and-healthy-controls
#1
Camila T Matsuzaka, Denise Christofolini, Vanessa K Ota, Ary Gadelha, Arthur A Berberian, Cristiano Noto, Diego R Mazzotti, Leticia M Spindola, Patricia N Moretti, Marilia A C Smith, Maria I Melaragno, Sintia I Belangero, Rodrigo A Bressan
Objective: Cognitive impairment is a core feature of schizophrenia, related to dopaminergic dysfunction in the prefrontal cortex (PFC). It is hypothesized that functional single nucleotide polymorphism (SNP) rs4680 of the catechol-O-methyltransferase (COMT) gene could mediate the relationship between cognition and dopamine activity in the PFC. Other COMT SNPs could also play a role. Methods: We evaluated the role of three COMT SNPs (rs737865, rs165599, and rs4680) in schizophrenia and their impact on three working memory tasks...
March 2, 2017: Revista Brasileira de Psiquiatria
https://www.readbyqxmd.com/read/28223811/risk-assessment-of-aggressive-behavior-in-chinese-patients-with-schizophrenia-by-fmri-and-comt-gene
#2
Xiaoli Tang, Jun Jin, Yi Tang, Jinbo Cao, Junjie Huang
BACKGROUND: Blood-oxygen-level dependent functional magnetic resonance imaging (BOLD-fMRI) maps cerebral activity by the hemodynamic response. Catechol-O-methyltransferase (COMT) gene is involved in the metabolism of dopamine. It is reported that both of these can be used to assess the aggression risk in patients with schizophrenia. However, these methods to assess the aggression risk patients with schizophrenia have not been established in China. Therefore, we deliver here a systematic review and meta-analysis based on the studies dealing with Chinese patients...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28202261/hyperprolinemia-as-a-clue-in-the-diagnosis-of-a-patient-with-psychiatric-manifestations
#3
Marco Duarte, Joana Afonso, Ana Moreira, Diana Antunes, Cristina Ferreira, Hildeberto Correia, Margarida Marques, Sílvia Sequeira
Lately, microdeletions of the 22q region, responsible for DiGeorge syndrome or velocardiofacial syndrome, have been increasingly related to neuropsychiatric disorders including schizophrenia and bipolar disorder. These manifestations seem to be related to certain genes located in the hemideleted region such as the proline dehydrogenase (PRODH) and the catechol-o-methyltransferase (COMT) genes. We describe a teenager who started his adolescent psychiatric care presenting cognitive impairment, irritable mood and aggressive behaviour with schizophrenia-like symptoms that scored 153 in the Positive and Negative Symptoms Scale (PANSS) assessment...
February 12, 2017: Brain & Development
https://www.readbyqxmd.com/read/28195063/generation-of-membrane-bound-catechol-o-methyl-transferase-deficient-mice-with-disctinct-sex-dependent-behavioral-phenotype
#4
A Tammimaki, A Aonurm-Helm, F P Zhang, M Poutanen, G Duran-Torres, A Garcia-Horsman, P T Mannisto
Catechol-O-methyltransferase (COMT) has two isoforms: soluble (S-COMT), which resides in the cytoplasm, and membrane-bound (MB-MT), anchored to intracellular membranes. COMT is involved in the O-methylation of L-DOPA, dopamine and other catechols. The exact role of MB-COMT is still mostly unclear. We wanted to create a novel genetically modified mouse model that specifically lacks MB-COMT activity and to study their behavioral phenotype. MB-COMT knock-in mutant mice were generated by introducing two point mutations in exon 2 of the Comt gene (ATGCTG->GAGCTC disabling the function of the P2 promoter and allowing only the P1-regulated S-COMT transcription...
December 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/27981425/-1-h-15-n-13-c-backbone-resonance-assignments-of-human-soluble-catechol-o-methyltransferase-in-complex-with-s-adenosyl-l-methionine-and-3-5-dinitrocatechol
#5
Sylwia Czarnota, Nicola J Baxter, Matthew J Cliff, Jonathan P Waltho, Nigel S Scrutton, Sam Hay
Catechol O-methyltransferase (COMT) is an enzyme that plays a major role in catechol neurotransmitter deactivation. Inhibition of COMT can increase neurotransmitter levels, which provides a means of treatment for Parkinson's disease, schizophrenia and depression. COMT exists as two isozymes: a soluble cytoplasmic form (S-COMT), expressed in the liver and kidneys and a membrane-bound form (MB-COMT), found mostly in the brain. Here we report the backbone (1)H, (15)N and (13)C chemical shift assignments of S-COMT in complex with S-adenosyl-L-methionine, 3,5-dinitrocatechol and Mg(2+)...
April 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/27685665/design-of-potent-and-druglike-nonphenolic-inhibitors-for-catechol-o-methyltransferase-derived-from-a-fragment-screening-approach-targeting-the-s-adenosyl-l-methionine-pocket
#6
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...
November 23, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27622935/evidence-that-comt-genotype-and-proline-interact-on-negative-symptom-outcomes-in-schizophrenia-and-bipolar-disorder
#7
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...
September 13, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27548835/dopamine-dysfunction-in-22q11-deletion-syndrome-possible-cause-of-motor-symptoms
#8
Livia Casarelli, Maurizio Minnei, Mariabernarda Pitzianti, Marco Armando, Maria Pontillo, Stefano Vicari, Augusto Pasini
22q11 Deletion syndrome (22q11DS) is a neurogenetic disorder, resulting from a hemizygous microdeletion on the long arm of chromosome 22. In 22q11DS, the phenotypic expression is highly variable. Approximately one-third of all individuals with 22q11DS develop schizophrenia-like psychotic disorder. Among the genes in the deleted region, catechol-O-methyltransferase (COMT) has a particular relevance for psychiatric disorders: lower COMT enzymatic activity decreases the clearance of dopamine (DA), yielding higher levels of catecholamines in the central nervous system...
October 2016: Psychiatric Genetics
https://www.readbyqxmd.com/read/27458023/manic-symptom-severity-correlates-with-comt-activity-in-the-striatum-a-post-mortem-study
#9
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...
April 2017: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/27421706/the-influence-of-the-comt-genotype-in-the-underlying-functional-brain-activity-of-context-processing-in-schizophrenia-and-in-relatives
#10
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
https://www.readbyqxmd.com/read/27315458/association-of-catechol-o-methyltransferase-val-108-158-met-genetic-polymorphism-with-schizophrenia-p50-sensory-gating-and-negative-symptoms-in-a-chinese-population
#11
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
https://www.readbyqxmd.com/read/27228319/a-tetra-primer-amplification-refractory-system-technique-for-the-cost-effective-and-novel-genotyping-of-eight-single-nucleotide-polymorphisms-of-the-catechol-o-methyltransferase-gene
#12
Cathy K Wang, Ana Aleksic, Michael S Xu, Ric M Procyshyn, Colin J Ross, Fidel Vila-Rodriguez, Alfredo Ramos-Miguel, Ryan Yan, William G Honer, Alasdair M Barr
AIMS: Catechol-O-methyltransferase (COMT) is an enzyme involved in the degradation of catecholamine neurotransmitters. Due to its role in neurotransmitter flux, multiple COMT variants have been associated with the development of psychiatric disorders. Notably, select single-nucleotide polymorphisms (SNPs) of the COMT gene have been implicated in schizophrenia risk, severity, and treatment response. In recognition of the value of a streamlined genotyping method for COMT SNP detection, this study was designed to develop a simple and economical tetra-primer amplification refractory mutation system (T-ARMS) assay for the concurrent detection of eight COMT SNPs: rs4680, rs737865, rs165599, rs2075507, rs4633, rs4818, rs6269, and rs165774...
August 2016: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/27021555/comt-val158met-polymorphism-and-molecular-alterations-in-the-human-dorsolateral-prefrontal-cortex-differences-in-controls-and-in-schizophrenia
#13
Abhay A Shukla, Manish Jha, Thomas Birchfield, Shibani Mukherjee, Kelly Gleason, Salim Abdisalaam, Aroumougame Asaithamby, Beverley Adams-Huet, Carol A Tamminga, Subroto Ghose
The single nucleotide val158met polymorphism in catechol o-methyltransferase (COMT) influences prefrontal cortex function. Working memory, dependent on the dorsolateral prefrontal cortex (DLPFC), has been repeatedly shown to be influenced by this COMT polymorphism. The high activity COMT val isoform is associated with lower synaptic dopamine levels. Altered synaptic dopamine levels are expected to lead to molecular adaptations within the synapse and within DLPFC neural circuitry. In this human post mortem study using high quality DLPFC tissue, we first examined the influence of the COMT val158met polymorphism on markers of dopamine neurotransmission, N-methyl-d-aspartate (NMDA) receptor subunits and glutamatic acid decarboxylase 67 (GAD67), all known to be critical to DLPFC circuitry and function...
May 2016: Schizophrenia Research
https://www.readbyqxmd.com/read/27020768/the-role-of-a-catechol-o-methyltransferase-comt-val158met-genetic-polymorphism-in-schizophrenia-a-systematic-review-and-updated-meta-analysis-on-32-816-subjects
#14
Thelma Beatriz González-Castro, Yazmin Hernández-Díaz, Isela Esther Juárez-Rojop, María Lilia López-Narváez, Carlos Alfonso Tovilla-Zárate, Ana Fresan
An association between a catechol-O-methyltransferase (COMT) Val156Met (rs4680) polymorphism and schizophrenia has been reported in the literature, although no conclusive outcomes have been attained. The aim of this study was to evaluate the association of the COMT Val108/158Met polymorphism with schizophrenia in a systematic review and meta-analysis. We performed a keyword search on PubMed and EBSCO databases. All English language case-control studies published up to April 2015 were selected. A total of 67 studies were selected for inclusion...
June 2016: Neuromolecular Medicine
https://www.readbyqxmd.com/read/26954460/comt-genotype-is-associated-with-differential-expression-of-muscarinic-m1-receptors-in-human-cortex
#15
Brian Dean, Elizabeth Scarr
Catechol-O-methyltransferase (COMT) genotype has been associated with varying levels of cognitive functioning and an altered risk of schizophrenia. COMT regulates the breakdown of catecholamines, particularly dopamine, which is thought critical in maintaining cognitive function and the aetiology of schizophrenia. This hypothesis gained support from reports that the VAL allele at rs4680 was associated with poorer performance on cognitive tests and a slightly increased risk of schizophrenia. More recently, genotype at rs4818, part of a hapblock with rs4680, has been shown to impact on cognitive ability more than genotype at rs4680 but, as yet, not the risk for schizophrenia...
September 2016: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/26864886/longitudinal-study-of-premorbid-adjustment-in-22q11-2-deletion-velocardiofacial-syndrome-and-association-with-psychosis
#16
Petya D Radoeva, Wanda Fremont, Kevin M Antshel, Wendy R Kates
Velocardiofacial syndrome, also known as 22q11.2 deletion syndrome (22q11DS), is associated with an increased risk of major psychiatric disorders, including schizophrenia. The emergence of psychotic symptoms in individuals with schizophrenia in the general population is often preceded by a premorbid period of poor or worsening social and/or academic functioning. Our current study evaluated premorbid adjustment (via the Cannon-Spoor Premorbid Adjustment Scale [PAS]) and psychotic symptoms (via the Structured Interview for Prodromal Symptoms and the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version) in youth with 22q11DS (N = 96), unaffected siblings (N = 40), and community controls (N = 50)...
February 2017: Development and Psychopathology
https://www.readbyqxmd.com/read/26852906/association-of-copy-number-polymorphisms-at-the-promoter-and-translated-region-of-comt-with-japanese-patients-with-schizophrenia
#17
Ryoko Higashiyama, Tohru Ohnuma, Yuto Takebayashi, Ryo Hanzawa, Nobuto Shibata, Hidenaga Yamamori, Yuka Yasuda, Itaru Kushima, Branko Aleksic, Kenji Kondo, Masashi Ikeda, Ryota Hashimoto, Nakao Iwata, Norio Ozaki, Heii Arai
Chromosome 22q11.2 deletion syndrome and genetic variations including single-nucleotide polymorphism (SNP) and copy number variation (CNV) in catechol-O-methyltransferase (COMT) situated at 22q11.2 remains controversial. Here, the genetic relationship between COMT and Japanese patients with schizophrenia was investigated by examining whether the SNPs correlated with schizophrenia based on a common disease-common variant hypothesis. Additionally, 22q11.2DS were screened based on a common disease-rare variant hypothesis; low-frequency CNVs situated at two COMT promoters and exons were investigated based on the low-frequency variants with an intermediate effect; and positive findings from the first stage were reconfirmed using a second-stage replication study including a larger sample size...
April 2016: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/26809779/dna-methylation-in-peripheral-tissue-of-schizophrenia-and-bipolar-disorder-a-systematic-review
#18
Nina Teroganova, Leah Girshkin, Catherine M Suter, Melissa J Green
BACKGROUND: Increasing evidence suggests the involvement of epigenetic processes in the development of schizophrenia and bipolar disorder, and recent reviews have focused on findings in post-mortem brain tissue. A systematic review was conducted to synthesise and evaluate the quality of available evidence for epigenetic modifications (specifically DNA methylation) in peripheral blood and saliva samples of schizophrenia and bipolar disorder patients in comparison to healthy controls. METHODS: Original research articles using humans were identified using electronic databases...
2016: BMC Genetics
https://www.readbyqxmd.com/read/26745992/catechol-o-methyltransferase-val158met-polymorphism-and-clinical-response-to-antipsychotic-treatment-in-schizophrenia-and-schizo-affective-disorder-patients-a-meta-analysis
#19
Eric Huang, Clement C Zai, Amanda Lisoway, Malgorzata Maciukiewicz, Daniel Felsky, Arun K Tiwari, Jeffrey R Bishop, Masashi Ikeda, Patricio Molero, Felipe Ortuno, Stefano Porcelli, Jerzy Samochowiec, Pawel Mierzejewski, Shugui Gao, Benedicto Crespo-Facorro, José M Pelayo-Terán, Harpreet Kaur, Ritushree Kukreti, Herbert Y Meltzer, Jeffrey A Lieberman, Steven G Potkin, Daniel J Müller, James L Kennedy
BACKGROUND: The catechol-O-methyltransferase (COMT) enzyme plays a crucial role in dopamine degradation, and the COMT Val158Met polymorphism (rs4680) is associated with significant differences in enzymatic activity and consequently dopamine concentrations in the prefrontal cortex. Multiple studies have analyzed the COMT Val158Met variant in relation to antipsychotic response. Here, we conducted a meta-analysis examining the relationship between COMT Val158Met and antipsychotic response...
May 2016: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/26560201/sex-dichotomous-effects-of-functional-comt-genetic-variations-on-cognitive-functions-disappear-after-menopause-in-both-health-and-schizophrenia
#20
Francesco Papaleo, Sara Sannino, Fabrizio Piras, Gianfranco Spalletta
Different genetic variations in the catechol-O-methyltransferase (COMT) gene have been indicated to functionally regulate the encoded enzyme. Despite the vast literature on the single nucleotide COMT ValMet polymorphism, the impact of complex haplotypes on cognitive functions has been overlooked. Here we contrasted the effects of complex COMT haplotypes with the ValMet polymorphism on cognitive functions and their interaction with menopause, in healthy subjects and patients with schizophrenia. Healthy adults (N=229) as well as patients with schizophrenia (N=172) underwent a comprehensive cognitive assessment taking into account the menopausal state...
December 2015: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
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