Anxiety is associated with higher levels of global DNA methylation and altered expression of epigenetic and interleukin-6 genes
Abstract
OBJECTIVES: Anxiety is associated with elevated levels of the inflammatory cytokine interleukin-6 (IL-6) and an increased risk for diseases with an inflammatory aetiology. In cancer, higher levels of IL-6 have been associated with increased expression of the epigenetic enzymes DNMT1 and Enhancer of Zeste Homolog 2 (EZH2). However, the relationship between IL-6 and DNA methyltransferases (DNMTs) and EZH2 expression has not previously been examined in anxious individuals. METHODS: Global DNA methylation levels were measured using the Methylflash Methylated DNA Quantification Kit and gene expression levels of the DNMT and EZH2 genes in anxious (n=25) and nonanxious individuals (n=22) were compared using quantitative real-time PCR. Specifically, we investigated whether global DNA methylation or aberrant expression of these genes was correlated with IL-6 mRNA and protein serum levels in anxious individuals. RESULTS: Anxious participants had significantly higher levels of global DNA methylation compared with controls (P=0.001). There were no differences in the mean mRNA expression levels of the DNMT1/3A/3B, EZH2 and IL-6 genes in anxious individuals compared with controls. However, the expression of DNMT1/3A, EZH2 and IL-6 genes increases with increasing Hospital Anxiety and Depression Scale-Anxiety scores in the anxious cohort only. Interestingly, IL-6 gene expression was correlated strongly with DNMT1/3A/3B and EZH2 expression, highlighting a potential relationship between IL-6 and important epigenetic regulatory enzymes. CONCLUSION: This study provides novel insight into the relationship between anxiety, epigenetics and IL-6. Moreover, our findings support the hypothesis that changes in DNA methylation profiles may contribute to the biology of anxiety.
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In anxious young adults, DNMT3a expression was significantly reduced in blood samples and correlated directly with anxiety severity.
“Previously, significantly reduced expression of DNMT3a was detected in blood samples retrieved from an anxious cohort consisting of young adults that correlated directly with anxiety severity (Murphy et al., 2015).”
From The Epigenetics of Anxiety Pathophysiology: A DNA Methylation and Histone Modification Focused Review (2023) · cites this paper as Murphy et al., 2015
Anxious individuals displayed higher levels of global methylation compared with nonanxious individuals, though site-specific methylation trends were not assessed.
“Individuals of the anxious cohort also displayed higher levels of global methylation compared with nonanxious individuals, though site-specific methylation trends were not assessed (Murphy et al., 2015).”
From The Epigenetics of Anxiety Pathophysiology: A DNA Methylation and Histone Modification Focused Review (2023) · cites this paper as Murphy et al., 2015
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- Authors
- Murphy, T. M., O’Donovan, A., Mullins, N., O’Farrelly, C., McCann, A., & Malone, K.
- Affiliations
- University College Dublin (IE)
- San Francisco VA Medical Center (US)
- St. Vincent's University Hospital (IE)
- Trinity College Dublin (IE)
- Corresponding author
- Murphy, Therese M.
- Venue
- Psychiatric Genetics
- Published
- 2015-04
- Volume
- 25
- Issue
- 2
- Pages
- 71-78
- ISSN
- 0955-8829 (ISSN-L)
- OpenAlex
- W2037651349
- Cited by
- 98
- References
- 6
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 5 · 2023: 7 · 2022: 13 · 2021: 5 · 2020: 7 · 2019: 12 · 2018: 10 · 2017: 16 · 2016: 8 · 2015: 3
- FWCI
- 3.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychiatric Genetics (publishedVersion)
- PubMed (publishedVersion)
- Royal Devon and Exeter Research Repository (Royal Devon and Exeter) (submittedVersion)
- Funders
- University College Dublin
- Trinity College Dublin
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- anxiety, global DNA methylation, interleukin-6, DNMT1, DNMT3A, DNMT3B, EZH2, epigenetic enzymes, gene expression, inflammation, DNA methyltransferases, anxiety biomarkers
- MeSH terms
- Enhancer of Zeste Homolog 2 Protein, DNA (Cytosine-5-)-Methyltransferase 1, DNA Methyltransferase 3A, DNA Methyltransferase 3B, Adult, Anxiety, DNA (Cytosine-5-)-Methyltransferases, Humans, Male, Manifest Anxiety Scale, Interleukin-6, DNA Methylation, Gene Expression Profiling, Epigenesis, Genetic, Polycomb Repressive Complex 2
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