Stress, burnout and depression: A systematic review on DNA methylation mechanisms
Open accessAbstract
Despite that burnout presents a serious burden for modern society, there are no diagnostic criteria. Additional difficulty is the differential diagnosis with depression. Consequently, there is a need to dispose of a burnout biomarker. Epigenetic studies suggest that DNA methylation is a possible mediator linking individual response to stress and psychopathology and could be considered as a potential biomarker of stress-related mental disorders. Thus, the aim of this review is to provide an overview of DNA methylation mechanisms in stress, burnout and depression. In addition to state-of-the-art overview, the goal of this review is to provide a scientific base for burnout biomarker research. We performed a systematic literature search and identified 25 pertinent articles. Among these, 15 focused on depression, 7 on chronic stress and only 3 on work stress/burnout. Three epigenome-wide studies were identified and the majority of studies used the candidate-gene approach, assessing 12 different genes. The glucocorticoid receptor gene (NR3C1) displayed different methylation patterns in chronic stress and depression. The serotonin transporter gene (SLC6A4) methylation was similarly affected in stress, depression and burnout. Work-related stress and depressive symptoms were associated with different methylation patterns of the brain derived neurotrophic factor gene (BDNF) in the same human sample. The tyrosine hydroxylase (TH) methylation was correlated with work stress in a single study. Additional, thoroughly designed longitudinal studies are necessary for revealing the cause-effect relationship of work stress, epigenetics and burnout, including its overlap with depression.
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The majority of findings relating to the epigenetics of psychosocial stressors and monoaminergic neurotransmission point towards hypermethylation of SLC6A4 and hypomethylation of MAOA, mirroring results in categorical analyses of MDD patients.
“Notably, the majority of findings relating to the epigenetics of psychosocial stressors and monoaminergic neurotransmission point towards a hypermethylation of SLC6A4 and a hypomethylation of MAOA, mirroring the results observed in categorical analyses of MDD patients (Bakusic, Schaufeli, Claes, & Godderis, 2017;Schiele et al., 2019), further stressing the need for longitudinal study designs”
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 Bakusic, Schaufeli, Claes, & Godderis, 2017
Methylation of NR3C1 may result in heightened gene expression, reduced PTG after trauma and dysfunctional HPA-axis function.
“Therefore, methylation of NR3C1 may result in heightened gene expression, reduced PTG after trauma and dysfunctional HPA-axis function.”
From DNA methylation of NR3C1 and FKBP5 is associated with posttraumatic stress disorder, posttraumatic growth, and resilience. (2020) · cites this paper as Bakusic et al., 2017
Methylation and expression of NR3C1 promotor associated regions has been consistently implicated in the pathophysiology of PTSD and other related disorders such as depression.
“This replicates previous findings where methylation and expression of NR3C1 promotor associated regions has been consistently implicated in the pathophysiology of PTSD and other related disorders such as depression (see Bakusic et al., 2017;Watkeys et al., 2018 reviews)”
From DNA methylation of NR3C1 and FKBP5 is associated with posttraumatic stress disorder, posttraumatic growth, and resilience. (2020) · cites this paper as Bakusic et al., 2017
These two different methylation patterns tend to increase gene expression, and have previously been associated with heightened distress and PTSD symptoms.
“These two different methylation patterns tend to increase gene expression (Bakusic et al., 2017;Dudley et al., 2011), and have previously been associated with heightened distress and PTSD symptoms (see Watkeys et al., 2018 review).”
From DNA methylation of NR3C1 and FKBP5 is associated with posttraumatic stress disorder, posttraumatic growth, and resilience. (2020) · cites this paper as Bakusic et al., 2017
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- Authors
- Bakusic, J., Schaufeli, W., Claes, S., & Godderis, L.
- Affiliations
- KU Leuven (BE)
- Universitair Ziekenhuis Leuven (BE)
- Corresponding author
- Bakusic, Jelena
- Venue
- Journal of Psychosomatic Research
- Publisher
- Elsevier BV
- Published
- 2017-01
- Volume
- 92
- Pages
- 34-44
- ISSN
- 0022-3999 (ISSN-L)
- OpenAlex
- W2550306825
- Cited by
- 223
- References
- 59
- Citations by year
- 2026: 15 · 2025: 22 · 2024: 22 · 2023: 33 · 2022: 25 · 2021: 25 · 2020: 40 · 2019: 14 · 2018: 20 · 2017: 7
- FWCI
- 1.24
- Type
- journal article
- Language
- en
- Open access
- Licence
- cc-by-nc-nd
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- Locations
- Journal of Psychosomatic Research (publishedVersion)
- PubMed (publishedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- Lirias (submittedVersion, cc-by-nc-nd)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Social Sciences › Psychology › Social Psychology › Stress and Burnout Research
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- DNA methylation, burnout, depression, chronic stress, occupational stress, epigenetic biomarkers, glucocorticoid receptor, NR3C1, serotonin transporter, brain-derived neurotrophic factor, tyrosine hydroxylase, candidate genes, epigenome-wide association study
- MeSH terms
- Animals, Burnout, Professional, Depression, Humans, Stress, Psychological, DNA Methylation
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