Differential effect of COMT gene methylation on the prefrontal connectivity in subjects with depression versus healthy subjects

Lee, Jin-Seong; Won, Eunsoo; Kang, June; Kim, Aram; Choi, Sun-Young; Tae, Woo Suk; Kim, Yong Ku; Lee, Min Soo; Joe, Sook Haeng; Ham, Byung Joo

doi:10.1016/j.neuropharm.2018.04.030

Cited by 45 publications

(15 citation statements)

References 59 publications

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“…These findings indicate that the expression of Comt gene can be regulated by dna methylation and hydroxymethylation in the brain. COMT is the primary regulator of dopamine clearance in extra-striatal regions of the brain, including the prefrontal cortex (13,41). elevated levels of coMT may accelerate the metabolism of dopamine and result in decreased dopamine levels, which may in turn influence brain function, potentially leading to depression.…”

Section: Discussionmentioning

confidence: 99%

“…a large amount of research has focused on a common, single nucleotide polymorphism of the COMT gene, Val158Met, which results in high activity of the coMT enzyme, contributing to the pathophysiology of major depressive disorder (Mdd) (11). Previous studies have suggested that methylation of the COMT gene impacts its subsequent expression (12,13). our previous study showed that phytochemically-stimulated COMT expression reversed the estrogen-induced inhibition of COMT via epigenetic mechanisms (14).…”

Section: Introductionmentioning

confidence: 99%

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Effects of caffeic acid on epigenetics in the brain of rats with chronic unpredictable mild stress

Cao

Zhang

et al. 2020

Mol Med Rep

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The present study hypothesized that caffeic acid (3,4-dihydroxycinnamic acid; caa) may exert antidepressant-like effects in rats with chronic unpredictable mild stress via epigenetic mechanisms, such as dna methylation and hydroxymethylation. The chronic unpredictable mild stress (cuMS) model was used to analyze the effects of caa on behavioral phenotypes, and to evaluate the distribution of 5-methylcytosine (5mc) and 5-hydroxymethylcytosine (5hmc) in the hippocampus and prefrontal cortex using immunohistochemistry and immunofluorescence. mrna levels of the genes encoding brain-derived neurotropic factor (BdnF) and catechol-o-methyltransferase (coMT), and key enzymes regulating dna methylation [dna methyltransferase (dnMT)1 and dnMT3a] and hydroxymethylation [Ten-eleven translocation (TeT)1-3] were examined using quantitative (q)Pcr. Furthermore, enrichment of 5mc and 5hmc at the promotor regions of the Bdnf and Comt genes was quantified using chromatin immunoprecipitation-qPcr. Behavioral data showed that caa exerted a slight antidepressant-like effect. Bdnf and Comt genes showed differential expression patterns due to cuMS. caa intervention induced different Dnmt1/Dnmt3a and Tet1/Tet2 mrna levels in the hippocampus and prefrontal cortex, respectively. caa regulated the ratio of 5mc/5hmc at the promotor region of the Bdnf and Comt genes and therefore influenced gene expression, which may be a valuable therapeutic option for major depressive disorder (Mdd). in conclusion, there were epigenetic changes in the hippocampus and prefrontal cortex in cuMS rats, and caa may function as a modulator of dna methylation to regulate gene transcription, thus providing a mechanistic basis for the use of this phytochemical agent in the treatment of Mdd.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of caffeic acid on epigenetics in the brain of rats with chronic unpredictable mild stress

Cao

Zhang

et al. 2020

Mol Med Rep

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“…Indeed, methylation of the COMT gene seems to produce different effects on the prefrontal connectivity in patients and controls. 7 The gene encoding the serotonin transporter also shows epigenetic changes that seem to be induced by environmental stressors in several disorders, such as major depression, bipolar disorder, PTSD, schizophrenia, attention deficit hyperactivity disorder (ADHD) and addiction. 2 The serotonin transporter takes the neurotransmitter back into the presynaptic terminal and is, of course, the site of action for selective serotonin reuptake inhibitors.…”

Section: Epigenetics and Depressionmentioning

confidence: 99%

Above genes: epigenetics and psychiatry

Greener¹

2019

Prog Neurol Psychiatry

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“…Interestingly, the prevailing hypothesis on prefrontal availability posits an inverted-U-shaped relationship between dopamine tone and prefrontal cognitive function, with both high and low dopamine levels being less advantageous than a moderate level (Witte and Floel, 2012). This relationship has been supported both by studies of cognitive performance with dopamine-enhancing interventions (Cai and Arnsten, 1997;Mattay et al, 2003) as well as in studies of neuropsychiatric conditions (Williams-Gray et al,2008;Na et al,2018). By this hypothesis, there is reason to suspect that the influence of COMT Val158Met on susceptibility to framing effects might differ in an older population with decreased dopamine signaling, as compared to a younger population.…”

Section: Introductionmentioning

confidence: 99%

COMT Val158Met polymorphism associated with greater susceptibility to framing effects in healthy older adults

Quinn

Borzello

Zahir

et al. 2019

Preprint

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Age-related neural changes may compromise older adults' decision-making, increasing their risk of fraud and financial abuse. One manifestation of nonrational influences on decision-making is susceptibility to "framing effects," in which decisions are biased by irrelevant contextual features of how choice information is presented. We investigated whether polymorphisms in genes related to dopamine neurotransmission (COMT) and neurodegeneration (ApoE) influence the susceptibility of older adults to framing effects. We administered an online test of susceptibility to framing effects to a cohort of 113 healthy older adults who had undergone genetic testing for COMT and ApoE genotype. The task required the participant to choose a risky or safe option in pairs of situations that were monetarily equivalent but differed in whether the choice was framed in terms of gains or losses. A general linear model was used to test for associations between inconsistency in choice across the set of choice pairs and these genotypes, controlling for age, education, gender and traditional measures of executive function. While no association to framing effects was found for ApoE, the Valine allele of COMT Val158Met was significantly associated with greater susceptibility to framing, although the association was no longer significant after adjustment for demographic covariates. Our results suggest that greater frontal dopamine concentrations associated with the COMT Met allele are protective against less consistent decision making in older adults. When compared to previous findings in young adults, our findings provide additional support for an inverted-U shaped model of prefrontal dopamine function.

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Differential effect of COMT gene methylation on the prefrontal connectivity in subjects with depression versus healthy subjects

Cited by 45 publications

References 59 publications

Effects of caffeic acid on epigenetics in the brain of rats with chronic unpredictable mild stress

Effects of caffeic acid on epigenetics in the brain of rats with chronic unpredictable mild stress

Above genes: epigenetics and psychiatry

COMT Val158Met polymorphism associated with greater susceptibility to framing effects in healthy older adults

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