BNDF methylation in mothers and newborns is associated with maternal exposure to war trauma

Abstract

BackgroundThe BDNF gene codes for brain-derived neurotrophic factor, a growth factor involved in neural development, cell differentiation, and synaptic plasticity. Present in both the brain and periphery, BDNF plays critical roles throughout the body and is essential for placental and fetal development. Rodent studies show that early life stress, including prenatal stress, broadly alters BDNF methylation, with presumed changes in gene expression. No studies have assessed prenatal exposure to maternal traumatic stress and BDNF methylation in humans. This study examined associations of prenatal exposure to maternal stress and BDNF methylation at CpG sites across the BDNF gene.ResultsAmong 24 mothers and newborns in the eastern Democratic Republic of Congo, a region with extreme conflict and violence to women, maternal experiences of war trauma and chronic stress were associated with BDNF methylation in umbilical cord blood, placental tissue, and maternal venous blood. Associations of maternal stress and BDNF methylation showed high tissue specificity. The majority of significant associations were observed in putative transcription factor binding regions.ConclusionsThis is the first study in humans to examine BDNF methylation in relation to prenatal exposure to maternal stress in three tissues simultaneously and the first in any mammalian species to report associations of prenatal stress and BDNF methylation in placental tissue. The findings add to the growing body of evidence highlighting the importance of considering epigenetic effects when examining the impacts of trauma and stress, not only for adults but also for offspring exposed via effects transmitted before birth.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-017-0367-x) contains supplementary material, which is available to authorized users.

The influence of aging on the methylation status of brain‐derived neurotrophic factor gene in blood

“…A wide body of evidences indicates the exposure to stressful events in adulthood changes DNAm in rodent brains. Several clinical studies have suggested the possibility that stressful events can alter DNAm of the BDNF gene in blood or brain . For example, we previously reported that DMRs in 28 of 35 CpG units at CpG I of the BDNF gene in blood were changed in unmedicated patients with major depression as compared with healthy subjects .…”

“…Several clinical studies have suggested the possibility that stressful events can alter DNAm of the BDNF gene in blood or brain. 33,34,40,41 For example, we previously reported that DMRs in 28 of 35 CpG units at CpG I of the BDNF gene in blood were changed in unmedicated patients with major depression as compared with healthy subjects. 28 Keller et al 42 reported that DMRs at the promoter of exon IV of the BDNF gene in the Wernicke area of subjects who had committed suicide Some limitations of the current study warrant mention.…”

Ageing and epigenetics: linking neurodevelopmental and neurodegenerative disorders

“…For example, BDNF is hypermethylated not only in mothers exposed to war trauma, but also in their new-born infants 29 and increased methylation of BDNF promoter is associated with conversion of amnestic mild cognitive impairment to Alzheimer disease. This is an area only recently starting to be explored, but one focus has been brain-derived neurotrophic factor.…”

“…This is an area only recently starting to be explored, but one focus has been brain-derived neurotrophic factor. For example, BDNF is hypermethylated not only in mothers exposed to war trauma, but also in their new-born infants 29 and increased methylation of BDNF promoter is associated with conversion of amnestic mild cognitive impairment to Alzheimer disease. 30 The genetics of Alzheimer disease is complex and, no doubt, the epigenetics is as well.…”

Trauma, Traumatization and Adverse Environments in War and Armed- Conflict

“…In this context, those individual soldiers who carried one or two low functioning alleles (the S or LG allele) reported enhanced symptoms of PTSD, depression and anxiety in response to increased levels of exposure to war zone stressors, relative to soldiers homozygous derived from the high functioning allele (LA allele). In a study of Among 24 mothers and newborn infants in the eastern Democratic Republic of Congo, a region afflicted by long-lasting, extreme conflict conditions of violence towards women and children, it was shown that the maternal experiences of war trauma and chronic stress were associated with BDNF methylation in umbilical cord blood, placental tissue, and maternal venous blood [29]. These linkages of maternal stress and BDNF methylation were associated with high tissue specificity with significant associations observed in the putative transcription factor binding regions of these individuals; a notable demonstration of detrimental epigenetic changes with long-lasting, trans-generational consequences.…”