BDNF Methylation and Maternal Brain Activity in a Violence-Related Sample

Abstract

It is known that increased circulating glucocorticoids in the wake of excessive, chronic, repetitive stress increases anxiety and impairs Brain-Derived Neurotrophic Factor (BDNF) signaling. Recent studies of BDNF gene methylation in relation to maternal care have linked high BDNF methylation levels in the blood of adults to lower quality of received maternal care measured via self-report. Yet the specific mechanisms by which these phenomena occur remain to be established. The present study examines the link between methylation of the BDNF gene promoter region and patterns of neural activity that are associated with maternal response to stressful versus non-stressful child stimuli within a sample that includes mothers with interpersonal violence-related PTSD (IPV-PTSD). 46 mothers underwent fMRI. The contrast of neural activity when watching children—including their own—was then correlated to BDNF methylation. Consistent with the existing literature, the present study found that maternal BDNF methylation was associated with higher levels of maternal anxiety and greater childhood exposure to domestic violence. fMRI results showed a positive correlation of BDNF methylation with maternal brain activity in the anterior cingulate (ACC), and ventromedial prefrontal cortex (vmPFC), regions generally credited with a regulatory function toward brain areas that are generating emotions. Furthermore we found a negative correlation of BDNF methylation with the activity of the right hippocampus. Since our stimuli focus on stressful parenting conditions, these data suggest that the correlation between vmPFC/ACC activity and BDNF methylation may be linked to mothers who are at a disadvantage with respect to emotion regulation when facing stressful parenting situations. Overall, this study provides evidence that epigenetic signatures of stress-related genes can be linked to functional brain regions regulating parenting stress, thus advancing our understanding of mothers at risk for stress-related psychopathology.

A longitudinal study of the associations of BDNF genotype and methylation with poststroke anxiety

“…Epigenetic studies have shown that DNA methylation regulates BDNF expression levels and that higher methylation status is associated with low BDNF expression . Accordingly, growing bodies of evidence suggest that BDNF hypermethylation is associated with anxiety in animal models and humans . Consistent with previous studies, the present findings demonstrated that BDNF hypermethylation was associated with anxiety in a stroke population.…”

“…Second, BDNF methylation may play a direct role in the development of anxiety only at 1 year after stroke. For example, BDNF methylation status is correlated with hippocampal activity in response to a stressor and has been linked to changes in BDNF mRNA levels during the fear conditioning, memory consolidation, and memory retrieval processes associated with the formation of anxiety . These processes are long lasting, and time‐dependent reorganization during the retrieval of fear memories has been observed .…”

“…Although few studies have investigated the associations of BDNF methylation with stroke and/or anxiety, one previous study found that increased BDNF methylation was associated with poor outcomes in stroke patients . In terms of anxiety, several studies of animal models showed that anxiety‐related behaviors were associated with BDNF hypermethylation; two studies that identified positive correlations between methylation and anxiety in humans were unable to establish the biological mechanisms underlying this association . Therefore, the present longitudinal study investigated the associations of BDNF methylation and polymorphisms with anxiety at 2 weeks and 1 year after stroke using a stroke cohort.…”

“…22 In terms of anxiety, several studies of animal models showed that anxiety-related behaviors were associated with BDNF hypermethylation [26][27][28] ; two studies that identified positive correlations between methylation and anxiety in humans were unable to establish the biological mechanisms underlying this association. 29,30 Therefore, the present longitudinal study investigated the associations of BDNF methylation and polymorphisms with anxiety at 2 weeks and 1 year after stroke using a stroke cohort. Additionally, this study examined the interaction between the BDNF Val66Met polymorphism and BDNF methylation in terms of the risk for PSA.…”

Neuroepigenetics of Post-Traumatic Stress Disorder

“…Summary of 43 human-based epigenetic studies of PTSD published as of July 2017, enumerated and categorized according to relevant biological system or Epigenome-wide association (EWAS) approach: Hypothalamic-Pituitary Adrenal (HPA) Axis 105,108,116,119,139–150 ; EWAS 91–96,151–155 ; Age-related CpGs 129,132,133 ; Serotonergic system 156,157 ; Neurotrophin 117,158 ; Dopaminergic System 159 ; Catecholaminergic system 102 ; DNA methylation machinery 160 ; Estrogen-responsive genes 114 ; Immune Function 161 ; Other 162–165 .…”