Abstract
Brain-derived neurotrophic factor (BDNF) plays a potential role in the neurobiology of burnout, but there are no studies investigating the underlying genetic and epigenetic mechanisms. Our aim is to further explore the role of BDNF in burnout, by focusing on the Val66Met polymorphism and methylation patterns of the BDNF gene and serum BDNF (sBDNF) protein expression. We conducted a cross-sectional study by recruiting 129 individuals (59 with burnout and 70 healthy controls). Participants underwent a clinical interview, psychological assessment and blood sample collection. Polymorphism and DNA methylation were measured on DNA from whole blood, using pyrosequencing and sBDNF levels were measured using ELISA. We found significantly increased methylation of promoter I and IV in the burnout group, which also correlated with burnout symptoms. In addition, DNA methylation of promoter I had a significant negative effect on sBDNF. For DNA methylation of exon IX, we did not find a significant difference between the groups, nor associations with sBDNF. The Val66Met polymorphism neither differed between groups, nor was it associated with sBDNF levels. Finally, we did not observe differences in sBDNF level between the groups. Interestingly, we observed a significant negative association between depressive symptoms and sBDNF levels. The current study is the first to show that BDNF DNA methylation changes might play an important role in downregulation of the BDNF protein levels in burnout. The presence of depressive symptoms might have an additional impact on these changes.
Highlights
Today, burnout has become one of the most widely discussed mental health problems in the workplace
In the present study we investigated the potential role of Brain-derived neurotrophic factor (BDNF) in burnout, by focusing on DNA methylation of specific regions and serum BDNF (sBDNF) protein levels
We observed a negative correlation between methylation of promoter I and sBDNF levels, confirming a silencing effect of DNA methylation in the promoter region
Summary
Burnout has become one of the most widely discussed mental health problems in the workplace. According to recent research conducted in Belgium, more than 7% of the working population have burnout complaints, whereas another 9% are “at risk” of developing burnout[2]. A recent literature review[1] shows that burnout research mainly focused on causes and associated factors, whereas studies on biological correlates are the least represented. The biological studies on burnout are heterogeneous in design, burnout assessment and laboratory techniques to quantify biomarkers, which make the Bakusic et al Translational Psychiatry (2020)10:354 comparison inconclusive[7]. There is no clear biological indicator for burnout that is sensitive and specific enough to confirm the diagnosis of burnout. The majority of studies focused on measurements of circulating proteins (mainly cortisol), but lack an indepth understanding of underlying molecular mechanisms affecting their expression[8]
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