Epigenetic impact of chronic stress: BDNF exon IV gene methylation in high-risk professionals

Stress is characterized by homeostatic imbalances caused by factors known as stressors. When faced with a stressor, the body activates the autonomic nervous system, the immune system, and the hypothalamic-pituitary-adrenal axis to restore homeostasis. Repeated exposure to stressful conditions can lead to epigenetic changes. Work-related stressors in high-pressure professions, can influence the epigenetics of key genes involved in brain function, including BDNF. This study investigated the relationship between BDNF DNA methylation and stress in military police officers. A total of 123 military police officers from Metropolitan Region of Grande Vitória, ES, Brazil were recruited to assess whether stress influences methylation by pyrosequencing the BDNF exon IV promoter region. A Generalized Linear Model was used to analyze the effect of stress on methylation levels, controlling for important confounding factors. The results showed that stress was significantly associated with BDNF DNA methylation at CpG 5, CpG 6, and CpG 11 in BDNF exon IV, a region that includes the binding site for the transcription factor CREB. These results indicate that the chance of occurrence of higher levels of methylation was 0.259 times higher at CpG 5, 0.471 times higher at CpG 6, and 0.461 times higher at CpG 11 in military police officers under stress than in those who did not experience stress. Based on these findings, we suggest that stress may act as an environmental pressure factor with implications for BDNF DNA methylation.