Psychological and biological risk factors of burnout – Investigating epigenetic risk scores to understand the mechanistic pathways from work-related stress to burnout

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According to the World Health Organization, work‐related stress forms a growing health burden and relates to tremendous costs in Western societies. A crucial condition in this context is burnout—a syndrome defined by emotional and physical exhaustion, negative attitudes toward work and negative evaluation of ones work performance that develops in response to chronically adverse working conditions. Today, it remains controversial whether burnout can be reliably distinguished from other stress-related disorders, most notably depression. Consequently, the identification of burnout-specific biomarkers constitutes a promising approach to understand the mechanistic pathways from work-related stress to burnout and to provide a biologically-informed basis for the distinction between burnout and depression. In this regard, epigenetic signatures such as DNA methylation have emerged as central mechanisms explaining how life stress may get under the skin. First cross-sectional findings in this field now call for prospective, longitudinal studies that ideally include high and low risk populations and combine fine-grained assessments of adversity and psychiatric symptoms with stress-related biomarkers. To address this gap, the Dresden Burnout Study (DBS) was initiated as a large-scale, 12-year prospective cohort study with annual assessment of burnout on a psychological, social, clinical, and biological level. In this proposal, we now aim to implement the assessment of epigenetic markers to complement and interpret the extensive multi-level data that has been obtained during the first waves of the DBS. Specifically, we aim to test the hypotheses that (a) work-related stress provokes a longitudinal trajectory of epigenetic changes that (b) predict immunological/endocrine dysregulation and burnout symptoms. To this end, we will estimate epigenetic risk scores (ERS) derived from summary statistics of prior epigenome-wide association studies on biological pathway by which stress may contribute to ensuing burnout symptoms (including cortisol output, inflammatory makers and epigenetic aging). Use of such ERS reflects a powerful strategy to aggregate small effects of single loci, which can then serve to robustly predict health phenotypes. Second, we seek to provide biologically-informed evidence for burnout’s discriminant validity by investigating whether specific ERS differentiate between burnout and depressive symptoms or not. Given that burnout, as compared to other stress-related disorders, has been assumed to first and foremost dependent on occupational adversity, we will illuminate whether (c) work-related stress provokes distinct longitudinal trajectory of ERS changes compared to non-work related stressors (d) that could differentiate burnout from depressive symptoms. Identifying objective risk biomarkers and specific pathological sequelae of burnout may deliver directions for developing personalized prevention and treatment strategies in the future.