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J Psychosom Res. 2017 Jan;92:34-44. doi: 10.1016/j.jpsychores.2016.11.005. Epub 2016 Nov 23.

Stress, burnout and depression: A systematic review on DNA methylation mechanisms.

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Environment and Health, Department of Public Health and Primary Care, KU Leuven, Kapucijnenvoer 35 blok d-box 7001, Belgium. Electronic address:
Work, Organisational and Personnel Psychology, Faculty of Psychology and Educational Sciences, KU Leuven, Dekenstraat 2-box 3725, Belgium. Electronic address:
Department of Psychiatry, University Hospital (UZLeuven) Leuven UZ,Herestraat 49-box 7003 37, Belgium. Electronic address:
Environment and Health, Department of Public Health and Primary Care, KU Leuven, Kapucijnenvoer 35 blok d-box 7001, Belgium; IDEWE, External Service for Prevention and Protection at Work, Interleuvenlaan 58, 3001, Heverlee, Belgium. Electronic address:


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.


Biomarker; Burnout; DNA methylation; Depression; Epigenetics; Stress

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