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.
Highlights
Children growing up in households with parents who were victims of violent trauma and who suffer from related psychopathology may themselves be at elevated risk for developmental psychopathology [1,2,3,4]
Consistent with the existing literature, the present study found that maternal Brain-Derived Neurotrophic Factor (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, regions generally credited with a regulatory function toward brain areas that are generating emotions
Since our stimuli focus on stressful parenting conditions, these data suggest that the correlation between ventromedial prefrontal cortex (vmPFC)/anterior cingulate cortex (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
Summary
Children growing up in households with parents who were victims of violent trauma and who suffer from related psychopathology (i.e. posttraumatic stress disorder [PTSD], major depressive disorder, and borderline personality disorder) may themselves be at elevated risk for developmental psychopathology [1,2,3,4]. It is known that elevated levels of circulating glucocorticoids induced by chronic stress interferes with BDNF signaling and increases anxiety [6]. Both BDNF and glucocorticoids regulate the release of Corticotrophin releasing factor in the hypothalamus [7]. Interactions and “crosstalks” likely exist between BDNF and NR3C1 gene expression in stress- related disorders. For example, predicted both infant NR3C1 and BDNF IV DNA methylation [8]
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