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Stress-Related Methylation of the Catechol- O -Methyltransferase Val 158 Allele Predicts Human Prefrontal Cognition and Activity
Open accessAbstract
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.
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In the citing paper
“In rats, a direct correlation between catechol-O-methyltransferase (COMT) methylation in peripheral mononuclear blood cells and the prefrontal cortex was observed (Ursini et al., 2011).”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Ursini et al., 2011
In the citing paper
“as several studies indicate its role in stress reactivity on a genetic [46,47] and epigenetic level [48].”
From Dynamic DNA methylation changes in the COMT gene promoter region in response to mental stress and its modulation by transcranial direct current stimulation (2021) · cites this paper as [48]
In the citing paper
“Indeed, for COMT DNAm several studies show that methylation status in peripheral tissue can serve as surrogate for brain DNAm [48,50].”
From Dynamic DNA methylation changes in the COMT gene promoter region in response to mental stress and its modulation by transcranial direct current stimulation (2021) · cites this paper as [48]
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“…also been recently shown to display a consistent methylation pattern between blood cells and caudate/cingulate cortex in human post-mortem tissue (Ursini et al., 2011) and changes in methylation observed in human blood samples within the COMT gene (Catechol-O-methyltransferase, a critical enzyme…”
BackgroundOxytocin receptor gene methylation: converging multilevel evidence for a role in social anxiety
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“For example, a recent fMRI study demonstrated that DNA methylation in the COMT gene measured in WBC predicted changes in brain activation patterns after stress exposure.(28) Here we hypothesized that that epigenetic mechanisms and individual variations in the sequence of the core promoter would modulate the epigenetic…”
BackgroundPredicting DNA methylation level across human tissues
Ma, B., Wilker, E. H., Willis‐Owen, S. A. G., Byun, H., Wong, K., Motta, V., Baccarelli, A., Schwartz, J. D., Cookson, W., Khabbaz, K. R., et al. (2014) · Nucleic Acids Research · doi:10.1093/nar/gkt1380 · Cited by 116
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“In a final example, a SNP in the COMT gene introduces a new CpG site and the methylation level of the variant allele is correlated with lifetime stress level and working memory [Ursini et al., 2011].”
BackgroundAntypa, N., Drago, A., & Serretti, A. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.06.006 · Cited by 120
Neurogenetics of depression: A focus on reward processing and stress sensitivity
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“These measures have”
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Hyde, L. W., Bogdan, R., & Hariri, A. R. (2011) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2011.07.001 · Cited by 107
Beyond the genome—Towards an epigenetic understanding of handedness ontogenesis
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“Reduced DNA methylation interacted with lifetime stress to modulate brain activity during a working memory task (Ursini et al., 2011).”
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“Epigenetic modifications via DNA methylation of the COMT promoter have been shown to regulate COMT expression (Ursini et al, 2011).”
Burris, H. H., Braun, J. M., Byun, H., Tarantini, L., Mercado, A., Wright, R. J., Schnaas, L., Baccarelli, A., Wright, R. O., & Téllez‐Rojo, M. M. (2013) · Epigenomics · doi:10.2217/epi.13.24 · Cited by 96
“demonstrated that DNA methylation that differed by genotype at C–T SNP loci can affect gene expression [52].”
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“For example, it was shown in one study that methylation patterns of the rodent catechol-O-methyltransferase gene were directly correlated in peripheral blood mononuclear cells and the prefrontal cortex (Ursini et al., 2011).”
BackgroundEpigenetics, Development, and Psychopathology
O'Donnell, K. J., & Meaney, M. J. (2020) · Annual Review of Clinical Psychology · doi:10.1146/annurev-clinpsy-050718-095530 · Cited by 94
“Studies combining human analyses with relevant model systems and focusing on candidate genomic regions can be informative (e.g., Kundakovic et al. 2015, Ursini et al. 2011).”
BackgroundDomschke, K., Tidow, N., Schrempf, M., Schwarte, K., Klauke, B., Reif, A., Kersting, A., Arolt, V., Zwanzger, P., & Deckert, J. (2013) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2013.07.014 · Cited by 87
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DNA methylation and brain structure and function across the life course: A systematic review
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“…DNAm at candidate genes, two reported that the sample used to measure DNAm was mononuclear blood cells (lymphocytes and monocytes) (Chouliaras et al., 2018; Ursini et al., 2011) whereas none of the studies that measured DNAm by bisulfite pyrosequencing reported correction for cell type composition.”
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“In a recent study, COMT polymorphism Val/ Val, analyzed in a cohort of healthy subjects, was found to be more sensitive to stress-related epigenetic changes and associated with more efficient working memory performance [67], [68].”
Wyns, A., Hendrix, J., Lahousse, A., Bruyne, E. D., Nijs, J., Godderis, L., & Polli, A. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12062245 · Cited by 91
Sensitive Periods in Epigenetics: Bringing us Closer to Complex Behavioral Phenotypes
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Epigenetic pathways through which experiences become linked with biology
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“Other reports helping to experimentally establish a link between epigenetic patterns and human brain function include one demonstrating that greater stress and lower methylation of the catechol-O-methyltransferase Val158 allele are correlated with more inefficient prefrontal activity (Ursini et al., 2011), and another…”
The future of fMRI and genetics research
Meyer‐Lindenberg, A. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2011.10.063 · Cited by 71
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Can we observe epigenetic effects on human brain function?
Nikolova, Y. S., & Hariri, A. R. (2015) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2015.05.003 · Cited by 73
Catechol-O-methyltransferase gene variation: Impact on amygdala response to aversive stimuli
Domschke, K., Baune, B. T., Havlik, L., Stuhrmann, A., Suslow, T., Kugel, H., Zwanzger, P., Grotegerd, D., Sehlmeyer, C., Arolt, V., et al. (2012) · NeuroImage · doi:10.1016/j.neuroimage.2012.02.039 · Cited by 69
“…in anxiety- and depression related phenotypes (Comasco et al., 2011; Conway et al., 2010; Kolassa et al., 2010; Mandelli et al., 2007) and methylation of the COMT 158val allele silencing COMT transcription to increase cortical efficiency in interaction with lifetime stress (Ursini et al., 2011).”
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“Of interest is recent evidence for epigenetic regulation of the COMT Val158 allele by lifetime stress exposure [30].”
Biological Effects of COMT Haplotypes and Psychosis Risk in 22q11.2 Deletion Syndrome
Gothelf, D., Law, A. J., Frisch, A., Chen, J., Zarchi, O., Michaelovsky, E., Ren‐Patterson, R. F., Lipska, B. K., Carmel, M., Kolachana, B. S., et al. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.07.021 · Cited by 70
“For example, methylation of CpG sites in the COMT promoter region have been shown to affect COMT expression in the brain and to be associated with risk for schizophrenia and prefrontal cognitive function (26,27).”
BackgroundCOMTVal158Met genotype is associated with reward learning: a replication study and meta‐analysis
Corral-Frías, N. S., Pizzagalli, D. A., Carré, J. M., Michalski, L. J., Nikolova, Y. S., Perlis, R. H., Fagerness, J. A., Lee, M. R., Drabant, E. M., Lancaster, T. M., et al. (2016) · Genes Brain & Behavior · doi:10.1111/gbb.12296 · Cited by 67
“Specifically, Val-allele homozygotes with low stress levels and heightened methylation in this region have working memory-related neural function and behavior comparable to Met-allele carriers highlighting the importance of considering methylation and stress in future COMT rs4680 genotype research (Ursini et al., 2011…”
BackgroundInfluentialWalton, E., Liu, J., Haß, J., White, T. J. H., Scholz, M. R., Roessner, V., Gollub, R. L., Calhoun, V. D., & Ehrlich, S. (2014) · Epigenetics · doi:10.4161/epi.29223 · Cited by 65
“Differences with respect to the direction of the methylation effect might be due to the location of the studied CpG (MB-COMT promoter in our study vs. exon 4 in the one by Ursini et al.).”
BackgroundInfluentialHumphreys, K. L., Moore, S. R., Davis, E., MacIsaac, J. L., Lin, D. T. S., Kobor, M. S., & Gotlib, I. H. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0582-7 · Cited by 70
Alcohol-induced plasticity in the dynorphin/kappa-opioid receptor system
SIROHI, S. K., Bakalkin, G. Y., & Walker, B. M. (2012) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2012.00095 · Cited by 68
“The mSNP hypothesis has also received support in several recent studies (John et al., 2011; Kaminsky et al., 2012; Martin-Trujillo et al., 2011; Reynard et al., 2011; Ursini et al., 2011).”
ResultBDNF rs6265 methylation and genotype interact on risk for schizophrenia
Ursini, G., Cavalleri, T., Fazio, L., Angrisano, T., Iacovelli, L., Porcelli, A., Maddalena, G., Punzi, G., Mancini, M., Gelao, B., et al. (2016) · Epigenetics · doi:10.1080/15592294.2015.1117736 · Cited by 62
“gous for the ancestral allele, but no association was found in heterozygotes.(5)”
BackgroundMethodInfluentialSelf-citationBastos, P., Gomes, T. M. B., & Ribeiro, L. V. P. T. (2017) · Reviews of physiology, biochemistry and pharmacology · doi:10.1007/112_2017_2 · Cited by 62
Genetic associations with performance on a behavioral measure of distress intolerance
Amstadter, A. B., Daughters, S. B., MacPherson, L., Reynolds, E. K., Danielson, C. K., Wang, F. M., Potenza, M. N., Gelernter, J. E., & Lejuez, C. W. (2011) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2011.09.017 · Cited by 60
Age modulates the effect of COMT genotype on delay discounting behavior
Smith, C. T., & Boettiger, C. A. (2012) · Psychopharmacology · doi:10.1007/s00213-012-2653-9 · Cited by 59
“Support for this possibility comes from recent data showing COMTval158met genotype-dependent methylation resulting in reduced val allele expression (Ursini et al. 2011).”
BackgroundAgreement in DNA methylation levels from the Illumina 450K array across batches, tissues, and time
Forest, M., O’Donnell, K. J., Voisin, G., Gaudreau, H., MacIsaac, J. L., McEwen, L. M., Silveira, P. P., Steiner, M. S., Kobor, M. S., Meaney, M. J., et al. (2018) · Epigenetics · doi:10.1080/15592294.2017.1411443 · Cited by 57
“We also examine in detail the DNA methylation patterns across individuals at six candidate genes that are the focus of many epigenetic studies in human psychology and psychiatry: OXTR, [20,21] DRD2, [22] DRD4, [23] COMT, [24] BDNF, [25] and SLC6A4 (alias HTTLPR) [26,27].”
BackgroundEffects of environmental noise exposure on DNA methylation in the brain and metabolic health
Guo, L., Li, P., Li, H., Colicino, E., Colicino, S., Wen, Y., Zhang, R., Feng, X., Barrow, T. M., Çayır, A., et al. (2016) · Environmental Research · doi:10.1016/j.envres.2016.11.017 · Cited by 59
“Catechol-O-methyltransferase (Comt), a key enzyme for inactivation of prefrontal dopamine (DA), has been found to be closely related with stress response, cognition, anxiety, and pain sensitivity (Gogos et al., 1998; Hains and Arnsten, 2008; Ursini et al., 2011; Papaleo et al., 2008).”
BackgroundSelf-citationMaternal prenatal anxiety and child COMT genotype predict working memory and symptoms of ADHD
O’Donnell, K. J., Glover, V. A. S., Lahti, J. M. T., Lahti‐Pulkkinen, M., Edgar, R. D., Räikkönen, K., & O’Connor, T. G. (2017) · PLoS ONE · doi:10.1371/journal.pone.0177506 · Cited by 59
Sex Differences in COMT Polymorphism Effects on Prefrontal Inhibitory Control in Adolescence
White, T. P., Loth, E., Rubia, K., Krabbendam, L., Whelan, R., Banaschewski, T., Barker, G. J., Bokde, A. L. W., Büchel, C., Conrod, P., et al. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.107 · Cited by 59
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“A recent fMRI study by Ursini et al.49 suggested that COMT and stress interacted through methylation, and this interaction tended to modulate prefrontal activities in a working memory task.”
BackgroundCRHR1 promoter hypomethylation: An epigenetic readout of panic disorder?
Schartner, C., Ziegler, C., Schiele, M. A., Kollert, L., Weber, H., Zwanzger, P., Arolt, V., Pauli, P., Deckert, J., Reif, A., et al. (2017) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2017.01.005 · Cited by 53
Pharmacoepigenetics of depression: no major influence of MAO-A DNA methylation on treatment response
Domschke, K., Tidow, N., Schwarte, K., Ziegler, C., Lesch, K., Deckert, J., Arolt, V., Zwanzger, P., & Baune, B. T. (2014) · Journal of Neural Transmission · doi:10.1007/s00702-014-1227-x · Cited by 56
COMT as a Drug Target for Cognitive Functions and Dysfunctions
Scheggia, D., Sannino, S., Scattoni, M. L., & Papaleo, F. (2012) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152712800672481 · Cited by 51
Neuroimaging genomics in psychiatry—a translational approach
Mufford, M. S., Stein, D. J., Dalvie, S., Groenewold, N. A., Thompson, P. M., & Jahanshad, N. (2017) · Genome Medicine · doi:10.1186/s13073-017-0496-z · Cited by 55
“ated almost two decades ago [2, 3], to recent breakthroughs made by global collaborations focused on GWAS [4], gene–gene effects [5], epigenetic findings [6], and gene–environment interactions [7] (Fig.”
BackgroundNa, K.-S., Won, E., Kang, J., Kim, A., Choi, S., Tae, W.-S., Kim, Y.-K., Lee, M.-S., Joe, S.-H., & Ham, B.-J. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.04.030 · Cited by 50
“Rodent studies have reported that the methylation status of the COMT gene in the peripheral blood correlated with that in the PFC (Ursini et al., 2011).”
Schiele, M. A., Zwanzger, P., Schwarte, K., Arolt, V., Baune, B. T., & Domschke, K. (2020) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyaa081 · Cited by 51
DNA Methylation in Schizophrenia Subjects: Gender and MTHFR 677C/T Genotype Differences
Burghardt, K. J., Pilsner, J. R., Bly, M. J., & Ellingrod, V. L. (2012) · Epigenomics · doi:10.2217/epi.12.25 · Cited by 49
Genetic Moderation of Stress Effects on Corticolimbic Circuitry
Bogdan, R., Pagliaccio, D., Baranger, D. A. A., & Hariri, A. R. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.216 · Cited by 53
“…PFC activation during N-back Greater stress predicts reduced methylation among Val homozygotes, which in turn predicts elevated PFC activation 84 Ursini et al, 2011 Moderate acute stress PFC activation during N-back Val carriers show blunted activation during control and elevated activation…”
BackgroundInfluentialLott, S. A., Burghardt, P. R., Burghardt, K. J., Bly, M. J., Grove, T. B., & Ellingrod, V. L. (2012) · The Pharmacogenomics Journal · doi:10.1038/tpj.2012.6 · Cited by 48
Wiers, C. E., Lohoff, F. W., Lee, J., Muench, C., Freeman, C. R., Zehra, A., Marenco, S., Lipska, B. K., Auluck, P. K., Feng, N., et al. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.14067 · Cited by 51
“…& Alexander, 2015); methylation of the Monoamine oxidase A (MAO-A) gene predicted MAO- A expression in brain (Shumay, Logan, Volkow, & Fowler, 2012), and Catechol- O- methyltransferase (COMT) methylation predicted prefrontal cortex activation on a working memory task (Ursini et al., 2011).”
BackgroundCiuculete, D. M., Boström, A. E., Voisin, S., Philipps, H., Titova, O. E., Bandstein, M., Nikontovic, L., Williams, M. J., Mwinyi, J., & Schiöth, H. B. (2017) · Translational Psychiatry · doi:10.1038/tp.2016.275 · Cited by 40
The DNA methylome in panic disorder: A case-control and longitudinal psychotherapy-epigenetic study
Ziegler, C., Grundner-Culemann, F., Schiele, M. A., Schlosser, P., Kollert, L., Mahr, M., Gajewska, A., Lesch, K.-P., Deckert, J., Köttgen, A., et al. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0648-6 · Cited by 47
Placental genomic risk scores and early neurodevelopmental outcomes
Ursini, G., Punzi, G., Langworthy, B., Chen, Q., Xia, K., Cornea, E. A., Goldman, B. D., Styner, M. A., Knickmeyer, R. C., Gilmore, J. H., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2019789118 · Cited by 46
Self-citationCannabis controversies: how genetics can inform the study of comorbidity
Arpana Agrawal, A., & Lynskey, M. T. (2014) · Addiction · doi:10.1111/add.12436 · Cited by 45
“Furthermore, there is evidence for stress-related methylation of the Val158 (rs4680) allele, which in turn, predicts aspects of human cognition, such as working memory (101).”
BackgroundHyde, L. W. (2015) · Development and Psychopathology · doi:10.1017/s0954579415000188 · Cited by 48
“Several studies have been published testing G E interactions that predict brain function, a critical first step in this emerging field (e.g., Cousijn et al., 2010; Drabant et al., 2012; Gerritsen et al., 2011; Ursini et al., 2011).”
BackgroundBoecker-Schlier, R., Holz, N. E., Buchmann, A. F., Blomeyer, D., Plichta, M. M., Jennen-Steinmetz, C., Wolf, I., Baumeister, S., Treutlein, J., Rietschel, M., et al. (2016) · NeuroImage · doi:10.1016/j.neuroimage.2016.02.006 · Cited by 42
Hernaus, D., Collip, D., Lataster, J., Ceccarini, J., Kenis, G., Booij, L., Pruessner, J. C., Laere, K. V., van Winkel, R., van Os, J., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0065662 · Cited by 41
“Interestingly, one such mechanism, Val-allele methylation, has been shown to crucially influence dopamine-mediated PFC activity in Val-homozygotes, but did not predict brain activity in Met-heterozygotes [34].”
BackgroundInfluentialPhysiological and behavioural responsivity to stress and anxiogenic stimuli in COMT-deficient mice
Desbonnet, L., Tighe, O., Karayiorgou, M., Gogos, J. A., Waddington, J. L., & O’Tuathaigh, C. M. P. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.12.014 · Cited by 38
Genetic Factors in Anxiety Disorders
Domschke, K., & Maron, E. (2013) · Modern trends in psychiatry · doi:10.1159/000351932 · Cited by 42
Swift‐Scanlan, T., Smith, C. T., Bardowell, S. A., & Boettiger, C. A. (2014) · BMC Medical Genomics · doi:10.1186/1755-8794-7-5 · Cited by 38
“Based on recent findings showing evidence of differential COMT DNA methylation [56], and associations between COMT methylation state and vulnerabilities to a spectrum of conditions ranging from schizophrenia [57,58] to the cognitive effects of stress [33], we sought to provide the first comprehensive assessment of DNA…”
BackgroundResultInfluentialImaging Epigenetics in Alzheimer’s Disease
Lista, S., Garaci, F. G., Toschi, N., & Hampel, H. J. (2013) · Current Pharmaceutical Design · doi:10.2174/13816128113199990370 · Cited by 36
“In an original study by Ursini and coworkers, imaging genetics methods were integrated with epigenetic markers in living humans [380].”
MethodGene x environment interactions in conduct disorder: Implications for future treatments
Holz, N. E., Zohsel, K., Laucht, M., Banaschewski, T., Hohmann, S., & Brandeis, D. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.08.017 · Cited by 35
Merrill, S. M., Gladish, N., Fu, M. P., Moore, S. R., Konwar, C., Giesbrecht, G. F., MacIssac, J. L., Kobor, M. S., & Letourneau, N. L. (2021) · Attachment & Human Development · doi:10.1080/14616734.2021.1938872 · Cited by 34
“Both SNP variation and DNAm within COMT have been associated with cognitive outcomes, especially in association with early life experience (Bruder et al., 2005; Malhotra et al., 2002; Ursini et al., 2011; Vidrascu et al., 2019; Walton et al., 2014).”
BackgroundDiwadkar, V. A., Bustamante, A. C., Rai, H., & Uddin, M. (2014) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2014.00071 · Cited by 29
“Additional analyses showed an interaction between methylation and stress scores on bilateral prefrontal activity during working memory, indicating that greater stress, when combined with lower methylation, are associated with greater activity (141).”
BackgroundInfluentialSarginson, J. E., Deakin, J. F. W., Anderson, I. M., Downey, D., Thomas, E., Elliott, R., & Juhász, G. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.137 · Cited by 29
Du, L., Merali, Z., Poulter, M. O., Palkovits, M., Faludi, G., & Anisman, H. (2014) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2013.12.016 · Cited by 29
“greater stress was associated with lower methylation of the Val158 allele in peripheral blood mononuclear cells of Val/Val individuals (Ursini et al., 2011).”
BackgroundMeta-analysis of the COMT Val158Met polymorphism in major depressive disorder: the role of gender
Klein, M., Schmoeger, M., Kasper, S. F., & Schosser, A. (2016) · The World Journal of Biological Psychiatry · doi:10.3109/15622975.2015.1083615 · Cited by 27
“The effect of COMT on depression might also be masked by epigenetic processes such as the genotypedependent methylation of the COMT Val158 allele modulating lifetime stress perception (Ursini et al. 2011), a significant contributor to the development of depressive states.”
BackgroundCarli, M. M. D., Baccarelli, A., Trevisi, L., Pantic, I., Brennan, K. J. M., Hacker, M. R., Loudon, H., Brunst, K. J., Wright, R. O., Wright, R. J., et al. (2017) · Epigenomics · doi:10.2217/epi-2016-0109 · Cited by 27
Self-citationNeuroepigenetics of Schizophrenia
Punzi, G., Bharadwaj, R. A., & Ursini, G. (2018) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2018.04.010 · Cited by 27
Self-citationVidrascu, E. M., Bashore, A. C., Howard, T. D., & Moore, J. B. (2019) · BMC Medical Genetics · doi:10.1186/s12881-019-0764-4 · Cited by 30
“In another study there was significantly reduced methylation at the site of the Val158 allele of the rs4680 single nucleotide polymorphism (Val158Met) in association with greater impairment in working memory performance [47].”
BackgroundMethodInfluentialMallick, R., & Duttaroy, A. K. (2023) · Neurochemistry International · doi:10.1016/j.neuint.2023.105627 · Cited by 27
Wei, J., Cheng, J., Waddell, N. J., Wang, Z.-J., Pang, X., Cao, Q., Liu, A., Chitaman, J. M., Abreu, K., Jasrotia, R. S., et al. (2020) · Cerebral Cortex · doi:10.1093/cercor/bhaa337 · Cited by 25
“…5 (FKBP5), Catechol-O-methyltransferase (COMT) and Spermidine/spermine N1-acetyl-transferase (SAT1), was found in the brain or blood samples from patients with PTSD or major depressive disorder or suicide subjects (Fiori and Turecki 2011; Ursini et al. 2011; Kang et al. 2013; Klengel et al. 2013).”
BackgroundAssociation between COMT methylation and response to treatment in children with ADHD
Fageera, W., Chaumette, B., Fortier, M., Grizenko, N., Labbe, A., Sengupta, S. M., & Joober, R. (2021) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2021.01.008 · Cited by 23
Reed, J. L., D’Ambrosio, E., Marenco, S., Ursini, G., Zheutlin, A. B., Blasi, G., Spencer, B. E., Romano, R., Hochheiser, J., Reifman, A., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0195189 · Cited by 26
Self-citationLewis, C. R., Henderson-Smith, A., Breitenstein, R. S., Sowards, H., Piras, I. S., Huentelman, M. J., Doane, L. D., & Lemery‐Chalfant, K. (2019) · Epigenetics · doi:10.1080/15592294.2019.1583032 · Cited by 24
“For example, genetic variation in theCOMT gene and stress interact with and influence methylation levels, which are associated with prefrontal activity and cognitive performance [74].”
BackgroundEpigenetics and the developmental origins of vulnerability for mental disorders
Meaney, M. J., & O’Donnell, K. J. (2015) · Wiley eBooks · doi:10.1002/9781118381953.ch25 · Cited by 23
Pap, D., Gonda, X., Molnár, E., Lazáry, J., Benkő, A., Downey, D., Thomas, E., Chase, D. S., Toth, Z. G., Mekli, K., et al. (2012) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32098 · Cited by 22
“As discussed in Introduction Section, COMT is required in the PFC to eliminate dopamine (DA) from the synaptic cleft; thus playing an important role in controlling DA levels [Chen et al., 2004].”
BackgroundInfluentialNeuroimaging Epigenetics: Challenges and Recommendations for Best Practices
Lancaster, K., Morris, J. P., & Connelly, J. J. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2017.08.004 · Cited by 23
Methylation and the human brain: towards a new discipline of imaging epigenetics
Wiers, C. E. (2011) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-011-0261-z · Cited by 21
Wiegand, A., Blickle, A., Brückmann, C., Weller, S., Nieratschker, V., & Plewnia, C. (2021) · Biomolecules · doi:10.3390/biom11111726 · Cited by 19
Gaysina, D., Xu, M. K., Barnett, J. H., Croudace, T. J., Wong, A., Richards, M., & Jones, P. B. (2012) · Biological Psychology · doi:10.1016/j.biopsycho.2012.11.007 · Cited by 20
Metadata
- Authors
- Ursini, G., Bollati, V., Fazio, L., Porcelli, A., Iacovelli, L., Catalani, A., Sinibaldi, L., Gelao, B., Romano, R., Rampino, A., Taurisano, P., Mancini, M., Di Giorgio, A., Popolizio, T., Baccarelli, A., De Blasi, A., Blasi, G., & Bertolino, A.
- Affiliations
- University of Bari Aldo Moro (IT)
- University of Milan (IT)
- Sapienza University of Rome (IT)
- Casa Sollievo della Sofferenza (IT)
- Harvard University (US)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-05-04
- Volume
- 31
- Issue
- 18
- Pages
- 6692-6698
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6632869
- OpenAlex
- W2008679805
- Cited by
- 188
- References
- 61
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 4 · 2023: 7 · 2022: 4 · 2021: 12 · 2020: 14 · 2019: 10 · 2018: 9 · 2017: 17 · 2016: 25 · 2015: 13 · 2014: 20 · 2013: 16 · 2012: 22
- FWCI
- 8.58
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- catechol-O-methyltransferase, DNA methylation, CpG, working memory, prefrontal cortex, gene silencing, epigenetics, peripheral blood mononuclear cells, gene expression, enzyme activity, rats
- MeSH terms
- Adult, Alleles, Animals, Catechol O-Methyltransferase, Cognition, Female, Genotype, Humans, Magnetic Resonance Imaging, Male, Memory, Short-Term, Neuropsychological Tests, Polymorphism, Genetic, Surveys and Questionnaires, Stress, Psychological, Blotting, Western, Rats, Wistar, Prefrontal Cortex, DNA Methylation, Reverse Transcriptase Polymerase Chain Reaction, Rats
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