ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Stress-related methylation of the catechol-O-methyltransferase Val 158 allele predicts human prefrontal cognition and activity.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 6 of them syntheses that pooled it.
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Who cites it
97 citing papers in PubMed, 6 syntheses or guidelines pooled it, 190 citations in OpenAlex.
- DNA methylation and brain structure and function across the life course: A systematic review.Neuroscience and biobehavioral reviews · 2020Pooled it
- Differences in Sensitivity to Environment Depending on Catechol-O-Methyltransferase (COMT) Gene? A Meta-analysis of Child and Adolescent Gene-by-Environment Studies.Journal of youth and adolescence · 2019Pooled it
- Effects of early- and mid-life stress on DNA methylation of genes associated with subclinical cardiovascular disease and cognitive impairment: a systematic review.BMC medical genetics · 2019Pooled it
- COMT Val(158) Met genotype is associated with reward learning: a replication study and meta-analysis.Genes, brain, and behavior · 2016Pooled it
- Maternal smoking during pregnancy and offspring conduct problems: evidence from 3 independent genetically sensitive research designs.JAMA psychiatry · 2013Pooled it
- Noise induced epigenetic effects: A systematic review.Noise & healthPooled it
- Epigenetic moderators of naltrexone efficacy in reducing heavy drinking in Alcohol Use Disorder: a randomized trial.The pharmacogenomics journal · 2022Trial
- COMT Val(158)Met genotype determines the direction of cognitive effects produced by catechol-O-methyltransferase inhibition.Biological psychiatry · 2012Trial
- Driven by Dopamine: Genetic Insights into Motivation and Performance in Sports and Esports.Genes · 2026Review
- Do common dopaminergic variants modulate processing speed in cognitive aging? A longitudinal candidate gene study.PloS one · 2026Article
- Review
- Intermediate endophenotypes and epigenetic mechanisms of psychiatric disorders.Imaging neuroscience (Cambridge, Mass.) · 2025Article
- Cognitive Impairments Related to COMT and Neuregulin 1 Phenotypes as Transdiagnostic Markers in Schizophrenia Spectrum Patients.Journal of clinical medicine · 2024Article
- Article
- The impact of placental genomic risk for schizophrenia and birth asphyxia on brain development.Translational psychiatry · 2023Article
- DNA Methylation Patterns in Relation to Acute Severity and Duration of Anxiety and Depression.Current issues in molecular biology · 2023Article
- The Biology of Stress Intolerance in Patients with Chronic Pain-State of the Art and Future Directions.Journal of clinical medicine · 2023Review
- Epigenetic MRI: Noninvasive imaging of DNA methylation in the brain.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Differences inFrontiers in genetics · 2022Article
- DNA Methylation as a Therapeutic and Diagnostic Target in Major Depressive Disorder.Frontiers in behavioral neuroscience · 2022Article
37 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.