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catechol-o-methyltransferase and schizophrenia

Ramin Saravani, Hamid Reza Galavi, Marzieh Lotfian Sargazi
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)...
October 2017: Iranian Journal of Psychiatry
Yikai Hu, Chenghu Li, Yangfan Wang, Qinhan Li, Yidong Liu, Shengde Liao, Peiqing Cao, Hongmei Xu
Schizophrenia is a severe mental disorder, and its mechanisms have not been fully elucidated. A functional single nucleotide polymorphism (SNP) present in the catechol-O-methyltransferase (COMT) gene, Val158Met (rs4680) (Chr22: 19,963,498), is possibly related to the violent behavior of schizophrenia patients. However, the specific variant that causes violent behavior is still unknown. Since the Val variation of Val158Met (rs4680) introduces a CG site into the sequence, the methylation level of the Val158Met (rs4680) region may also have an association with the homicidal behavior of schizophrenia patients...
February 17, 2018: International Journal of Legal Medicine
Anna V Kirenskaya, Zinaida I Storozheva, Marina A Gruden, Robert D E Sewell
Genetic influences modulating executive functions engaging prefrontal cortical brain systems were investigated in 141 male subjects. The effects of variations in two genes implicated in dopamine and GABA activities in the prefrontal cortex: rs4680 (Val158/Met polymorphism of the catechol-o-methyltransferase gene-COMT) and rs3749034 (C/T) substitution in the promoter region of the glutamic acid decarboxylase gene (GAD1) were studied on antisaccade (AS) performance in healthy subjects and schizophrenic patients...
February 10, 2018: European Archives of Psychiatry and Clinical Neuroscience
Claudia Schilling, Lena Gappa, Michael Schredl, Fabian Streit, Jens Treutlein, Josef Frank, Michael Deuschle, Andreas Meyer-Lindenberg, Marcella Rietschel, Stephanie H Witt
Study Objectives: Sleep spindles are a hallmark of NREM stage 2 sleep. Fast sleep spindles correlate with cognitive functioning, and are reduced in schizophrenia. Although spindles are highly genetically determined, distinct genetic mechanisms influencing sleep spindle activity have not been identified so far. Spindles are generated within a thalamo-cortical network. Dopaminergic neurotransmission modulates activity within this network and importantly depends on activity of catechol-O-methyltransferase (COMT)...
January 6, 2018: Sleep
Abd Rahim Nour El Huda, Ku Zaifah Norsidah, Rahim Mohd Nabil Fikri, Mohd Noor Hanisah, Abdullah Kartini, A Talib Norlelawati
AIM: This study examined catechol-O-methyltransferase (COMT) DNA methylation in the peripheral blood of schizophrenia patients and also in healthy controls to investigate its potential use as a peripheral biomarker of schizophrenia and its relationships with the clinical variables of schizophrenia patients. METHODS: We examined the DNA methylation levels of COMT using genomic DNA from the peripheral blood of schizophrenia patients (n = 138) and healthy control participants (n = 132); all were Malaysian Malays...
November 21, 2017: Psychiatry and Clinical Neurosciences
Neal R Swerdlow, Savita G Bhakta, Jo A Talledo, Daniel M Franz, Erica L Hughes, Brinda K Rana, Gregory A Light
Prepulse inhibition (PPI) of startle is being explored both as an indicator of target engagement for, and a biomarker predicting the sensitivity to, procognitive effects of drugs. We now report the effects of the pro-attentional drug, d-amphetamine, on PPI and neurocognition in antipsychotic-medicated schizophrenia patients and healthy subjects (HS) who were also tested in a targeted cognitive training (TCT) module. 44 HS and 38 schizophrenia patients completed a double-blind, placebo-controlled crossover study of the effects of a single dose of amphetamine (10 mg po) on PPI and MATRICS Consensus Cognitive Battery (MCCB) performance; TCT results were previously reported from 60 of these subjects...
March 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Giuseppe Carrà, Gabriella Nicolini, Annamaria Lax, Francesco Bartoli, Filippo Castellano, Alessia Chiorazzi, Giulia Gamba, Mattia Bava, Cristina Crocamo, Costanza Papagno
OBJECTIVES: 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. METHODS: 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...
September 15, 2017: Human Psychopharmacology
Aneta Tylec, Witold Jeleniewicz, Ann Mortimer, Małgorzata Bednarska-Makaruk, Katarzyna Kucharska
The Val158Met catechol-O-methyltransferase (COMT) functional polymorphism may influence social cognitive functioning in patients with schizophrenia. Aspects of social cognition were evaluated with the Facial Expression Recognition Test, the Voice Emotion Recognition Test, and the Reading the Mind in the Eyes Test. The Short Recognition Memory Test for Faces was used as a control measure. The Schedule for the Assessment of Negative Symptoms, Schedule for the Assessment of Positive Symptoms, and Beck Depression Inventory were used to rate of patient symptoms...
August 30, 2017: Annals of Human Genetics
Błażej Misiak, Filip Stramecki, Łukasz Gawęda, Katarzyna Prochwicz, Maria M Sąsiadek, Ahmed A Moustafa, Dorota Frydecka
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...
August 18, 2017: Molecular Neurobiology
Giuseppe Carrà, Gabriella Nicolini, Cristina Crocamo, Annamaria Lax, Francesca Amidani, Francesco Bartoli, Filippo Castellano, Alessia Chiorazzi, Giulia Gamba, Costanza Papagno, Massimo Clerici
BACKGROUND: 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. METHODS: 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)...
February 14, 2017: Nordic Journal of Psychiatry
Steven Taylor
Catechol-O-methyltransferase (COMT) Val158Met is widely regarded as potentially important for understanding the genetic etiology of many different psychiatric disorders. The present study appears to be the first comprehensive meta-analysis of COMT genetic association studies to cover all psychiatric disorders for which there were available data, published in any language, and with an emphasis on investigating disorder subtypes (defined clinically or by demographic or other variables). Studies were included if they reported one or more datasets (i...
June 13, 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
J-C Debost, M Debost, J Grove, O Mors, D M Hougaard, A D Børglum, P B Mortensen, L Petersen
OBJECTIVE: Mesolimbic dopamine sensitization has been hypothesized to be a mediating factor of childhood adversity (CA) on schizophrenia risk. Activity of catechol-O-methyltransferase (COMT) Val158Met increases mesolimbic dopamine signaling and may be further regulated by methylenetetrahydrofolate reductase (MTHFR) C677T. This study investigates the three-way interaction between CA, COMT, and MTHFR. METHODS: We conducted a nested case-control study on individuals born after 1981, linking population-based registers to study the three-way interaction...
July 2017: Acta Psychiatrica Scandinavica
S Gao, J Cheng, G Li, T Sun, Y Xu, Y Wang, X Du, G Xu, S Duan
As an epigenetic modification, DNA methylation may reflect the interaction between genetic and environmental factors in the development of schizophrenia (SCZ). Catechol-O-methyltransferase (COMT) gene is a promising candidate gene of SCZ. In the present study, we investigate the association of COMT methylation with the risk of SCZ using bisulfite pyrosequencing technology. Significant association between DNA methylation of COMT and the risk of SCZ is identified (P=1.618e-007). A breakdown analysis by gender shows that the significance is driven by males (P=3...
March 30, 2017: European Psychiatry: the Journal of the Association of European Psychiatrists
Kristel Klaus, Kevin Butler, Simon J Durrant, Manir Ali, Chris F Inglehearn, Timothy L Hodgson, Humberto Gutierrez, Kyla Pennington
INTRODUCTION: 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...
May 2017: Brain and Behavior
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
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
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...
June 2017: Brain & Development
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
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
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
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