Methylation of NR3C1 is related to maternal PTSD, parenting stress and maternal medial prefrontal cortical activity in response to child separation among mothers with histories of violence exposure

Abstract

Prior research has shown that mothers with Interpersonal violence-related posttraumatic stress disorder (IPV-PTSD) report greater difficulty in parenting their toddlers. Relative to their frequent early exposure to violence and maltreatment, these mothers display dysregulation of their hypothalamic pituitary adrenal axis (HPA-axis), characterized by hypocortisolism. Considering methylation of the promoter region of the glucocorticoid receptor gene NR3C1 as a marker for HPA-axis functioning, with less methylation likely being associated with less circulating cortisol, the present study tested the hypothesis that the degree of methylation of this gene would be negatively correlated with maternal IPV-PTSD severity and parenting stress, and positively correlated with medial prefrontal cortical (mPFC) activity in response to video-stimuli of stressful versus non-stressful mother–child interactions. Following a mental health assessment, 45 mothers and their children (ages 12–42 months) participated in a behavioral protocol involving free-play and laboratory stressors such as mother–child separation. Maternal DNA was extracted from saliva. Interactive behavior was rated on the CARE-Index. During subsequent fMRI scanning, mothers were shown films of free-play and separation drawn from this protocol. Maternal PTSD severity and parenting stress were negatively correlated with the mean percentage of methylation of NR3C1. Maternal mPFC activity in response to video-stimuli of mother–child separation versus play correlated positively to NR3C1 methylation, and negatively to maternal IPV-PTSD and parenting stress. Among interactive behavior variables, child cooperativeness in play was positively correlated with NR3C1 methylation. Thus, the present study is the first published report to our knowledge, suggesting convergence of behavioral, epigenetic, and neuroimaging data that form a psychobiological signature of parenting-risk in the context of early life stress and PTSD.

Association between theta power in 6-month old infants at rest and maternal PTSD severity: A pilot study

“…Perinatal PTSD affects emotional and physiological development of infants [7,8], perhaps via maternal corticolimbic dysregulation [9] or impaired responsiveness [10]. Relative to infants born to mothers without PTSD, infants born to mothers with perinatal PTSD face poorer emotional regulation and behavioral reactivity [7] and increased symptom severity if they develop PTSD later [8].…”

Maternal Neurobiological Processing of Negative Adolescent Stimuli: Relations With Positive Parenting and Relationship Quality

“…In one study of first time mothers and their 18‐month old infants, mother's with infants showing insecure attachment behaviors recruited less dorsolateral prefrontal cortex (dlPFC) and orbitofrontal cortex and other prefrontal areas (dorsal anterior cingulate cortex [ACC], medial superior frontal regions) than mothers of securely attached infants in response to infant crying (Laurent & Ablow, ). Other studies have shown similar patterns, with greater maternal prefrontal recruitment (e.g., dlPFC, medial PFC, inferior frontal gyrus) in response to neutral and negative child stimuli relating to less parenting stress (Schechter et al., ), higher maternal sensitivity (Musser, Kaiser‐Laurent & Ablow, ), higher positive parenting (Michalska et al., ), and a history of higher quality maternal care experienced during a mother's own childhood (Kim et al., ).…”

Single‐nucleotide polymorphisms in genes related to the hypothalamic‐pituitary‐adrenal axis as risk factors for posttraumatic stress disorder

“…Many studies suggest that alterations in NR3C1 (Glucocorticoid Receptor gene) methylation due to changes in the HPA axis may be associated with environmental exposures in PTSD (Bockmühl et al, ; Perroud et al, ; Schechter et al, ; Yehuda et al, ). Other studies found that methylation of CRHR1 (Corticotropin Releasing Hormone Type 1 Receptor), FKBP5 (FK506 Binding Protein 5 gene), SLC6A3 (solute carrier family 6 member 3) and SLC6A4 (solute carrier family 6 member 4), and IGF2 (insulin like growth factor 2) genes may be associated to the pathogenesis of PTSD (McGowan, ; Zannas et al, ).…”