ArticleFrontiers in behavioral neuroscience2013
Differential Genetic and Epigenetic Regulation of catechol-O-methyltransferase is Associated with Impaired Fear Inhibition in Posttraumatic Stress Disorder.
Article in Frontiers in behavioral neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
48 citing papers in PubMed, 2 syntheses or guidelines pooled it, 104 citations in OpenAlex.
- Pooled it
- The Association Between Genetic Variants in the Dopaminergic System and Posttraumatic Stress Disorder: A Meta-Analysis.Medicine · 2016Pooled it
- Article
- The clinical use of epigenetics in psychiatry: a narrative review of epigenetic mechanisms, key candidate genes, and precision psychiatry.Frontiers in psychiatry · 2025Review
- Fear extinction rescuing effects of dopamine and L-DOPA in the ventromedial prefrontal cortex.Translational psychiatry · 2024Article
- Effects of a True Prophylactic Treatment on Hippocampal and Amygdala Synaptic Plasticity and Gene Expression in a Rodent Chronic Stress Model of Social Defeat.International journal of molecular sciences · 2023Article
- Ventral Tegmental Area Dysfunction and Disruption of Dopaminergic Homeostasis: Implications for Post-traumatic Stress Disorder.Molecular neurobiology · 2021Review
- DAT1 and Its Psychological Correlates in Children with Avoidant/Restrictive Food Intake Disorder: A Cross-Sectional Pilot Study.Behavioral sciences (Basel, Switzerland) · 2021Article
- Corticosterone Treatment and Incubation Time After Contextual Fear Conditioning Synergistically Induce Fear Memory Generalization in Neuropeptide S Receptor-Deficient Mice.Frontiers in neuroscience · 2020Article
- The temporal course of over-generalized conditioned threat expectancies in posttraumatic stress disorder.Behaviour research and therapy · 2020Article
- Prolonged febrile seizures induce inheritable memory deficits in rats through DNA methylation.CNS neuroscience & therapeutics · 2019Article
- Stress Across Generations: DNA Methylation as a Potential Mechanism Underlying Intergenerational Effects of Stress in Both Post-traumatic Stress Disorder and Pre-clinical Predator Stress Rodent Models.Frontiers in behavioral neuroscience · 2019Article
- Therapeutic Challenges of Post-traumatic Stress Disorder: Focus on the Dopaminergic System.Frontiers in pharmacology · 2019Review
- REM sleep and safety signal learning in posttraumatic stress disorder: A preliminary study in military veterans.Neurobiology of stress · 2018Article
- Traumatic Stress Epigenetics.Current behavioral neuroscience reports · 2018Article
- COMT val158met polymorphism links to altered fear conditioning and extinction are modulated by PTSD and childhood trauma.Depression and anxiety · 2018Article
- Catecholamines in Post-traumatic Stress Disorder: A Systematic Review and Meta-Analysis.Frontiers in molecular neuroscience · 2018Article
- Neuroepigenetics of Post-Traumatic Stress Disorder.Progress in molecular biology and translational science · 2018Review
- Whole-genome DNA methylation status associated with clinical PTSD measures of OIF/OEF veterans.Translational psychiatry · 2017Article
- The genetics of anxiety-related negative valence system traits.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2017Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
The catechol-O-methyltransferase (COMT) enzyme is critical for the catabolic regulation of synaptic dopamine, resulting in altered cortical functioning. The COMT Val(158)Met polymorphism has been implicated in human mental illness, with Met/Met homozygotes associated with increased susceptibility to posttraumatic stress disorder (PTSD). Our primary objective was to examine the intermediate phenotype of fear inhibition in PTSD stratified by COMT genotype (Met/Met, Val/Met, and Val/Val) and differential gene regulation via methylation status at CpG sites in the COMT promoter region. More specifically, we examined the potential interaction of COMT genotype and PTSD diagnosis on fear-potentiated startle during fear conditioning and extinction and COMT DNA methylation levels (as determined using genomic DNA isolated from whole blood). Participants were recruited from medical and gynecological clinics of an urban hospital in Atlanta, GA, USA. We found that individuals with the Met/Met genotype demonstrated higher fear-potentiated startle to the CS- (safety signal) and during extinction of the CS+ (danger signal) compared to Val/Met and Val/Val genotypes. The PTSD+ Met/Met genotype group had the greatest impairment in fear inhibition to the CS- (p = 0.006), compared to Val carriers. In addition, the Met/Met genotype was associated with DNA methylation at four CpG sites, two of which were associated with impaired fear inhibition to the safety signal. These results suggest that multiple differential mechanisms for regulating COMT function - at the level of protein structure via the Val(158)Met genotype and at the level of gene regulation via differential methylation - are associated with impaired fear inhibition in PTSD.
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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.