Childhood adverse events and BDNF promoter methylation in later-life

Abstract

Studies have shown that the effects of early-life stress and trauma can be enduring, with long-term negative effects on health. Epigenetics, including DNA methylation, have been implicated as a potential mechanism for these effects. Brain-derived neurotropic factor (BDNF) is a neurotransmitter involved in learning and memory, and altered BDNF promoter methylation measured in peripheral tissue has been found with early-life stress. However, whether such methylation differences remain stable into later life, is unknown. This study aimed to investigate the association between childhood adversity and BDNF promoter methylation in adults aged 65 years and over. Data came from a large study of older community-dwelling individuals in France (ESPRIT). Information on three major childhood adverse events, namely abuse/maltreatment, war/natural disaster, and financial difficulties/poverty, was obtained by retrospective reporting from participants of ESPRIT study. BDNF promoter I and IV methylation was assessed in blood and buccal tissue. Linear regression analysis was performed, adjusting for age, sex, education, depression, and morbidity. Among 927 participants, there was no strong evidence that childhood abuse/maltreatment or financial difficulties/poverty were associated with BDNF methylation in older individuals. For war/natural disaster, differential methylation at four of twenty-nine CpG sites was observed, however, these would not have remained significant after correction for multiple testing. Together, these findings do not support a long-term association between adverse childhood events and BDNF methylation in older age, but further large prospective studies are needed, which do not target specific genes, but consider DNA methylation across the genome.

Association of hair cortisol concentration with brain‐derived neurotrophic factor gene methylation: The role of sex as a moderator

“…Taken together with the previous result (Fransquet et al, 2022;Unternaehrer et al, 2012;Zhou et al, 2023), our findings suggest the role of BDNF DNA M in the biological response to daily life stressors.…”

“…In the case of early-life stress, the level of BDNF DNA M in rats increased in response to early-life adversity, and this increase persisted into adulthood (Zhou et al, 2023). The current study finding of the association of BDNF DNA M with HCC supplements the previous findings (Unternaehrer et al, 2012;Zhou et al, 2023) by demonstrating that the level of BDNF DNA M in young adults increased in accordance with the HPA axis activity on a long-term basis. In regard to the relationship between BDNF DNA M and cortisol, BDNF DNA M was reported to be positively associated with morning cortisol levels in the offspring of mothers diagnosed with PTSD during pregnancy (Fransquet et al, 2022).…”

“…Regarding the relations between BDNF DNA M and stress response according to the time of stressor exposure, BDNF DNA M has been reported to remain stable in cases of acute stress, such as threat to social self, during the social stress test (Unternaehrer et al, 2012). In the case of early-life stress, the level of BDNF DNA M in rats increased in response to early-life adversity, and this increase persisted into adulthood (Zhou et al, 2023). The current study finding of the association of BDNF DNA M with HCC supplements the previous findings (Unternaehrer et al, 2012;Zhou et al, 2023) by demonstrating that the level of BDNF DNA M in young adults increased in accordance with the HPA axis activity on a long-term basis.…”