Francesca Suardi

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.

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.

BDNF methylation and maternal brain activity in a violence-related sample

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.

The association of serotonin receptor 3A methylation with maternal violence exposure, neural activity, and child aggression ☆

Background Methylation of the serotonin 3A receptor gene (HTR3A) has been linked to child maltreatment and adult psychopathology. The present study examined whether HTR3A methylation might be associated with mothers’ lifetime exposure to interpersonal violence (IPV), IPV‐related psychopathology, child disturbance of attachment, and maternal neural activity. Methods Number of maternal lifetime IPV exposures and measures of maternal psychopathology including posttraumatic stress disorder (PTSD), major depression and aggressive behavior (AgB), and a measure of child attachment disturbance known as “secure base distortion” (SBD) were assessed in a sample of 35 mothers and children aged 12–42 months. Brain fMRI activation was assessed in mothers using 30‐s silent film excerpts depicting menacing adult male‐female interactions versus prosocial and neutral interactions. Group and continuous analyses were performed to test for associations between clinical and fMRI variables with DNA methylation. Results Maternal IPV exposure‐frequency was associated with maternal PTSD; and maternal IPV‐PTSD was in turn associated with child SBD. Methylation status of several CpG sites in the HTR3A gene was associated with maternal IPV and IPV‐PTSD severity, AgB and child SBD, in particular, self‐endangering behavior. Methylation status at a specific CpG site (CpG2_III) was associated with decreased medial prefrontal cortical (mPFC) activity in response to film‐stimuli of adult male‐female interactions evocative of violence as compared to prosocial and neutral interactions. Conclusions Methylation status of the HTR3A gene in mothers is linked to maternal IPV‐related psychopathology, trauma‐induced brain activation patterns, and child attachment disturbance in the form of SBD during a sensitive period in the development of self‐regulation. HighlightsMaternal severity of interpersonal violence exposure (IPV) was associated with diagnosis of maternal post‐traumatic stress disorder (PTSD).Maternal IPV‐PTSD was in turn associated with disturbed child attachment.HTR3A gene methylation was linked to maternal IPV exposure and aggressive behavior and disturbed child attachment and self‐endangering behavior.HTR3A methylation at the CpG2_III site was linked to decreased medial prefrontal cortical activity in response to menacing relational stimuli.

The relation of general socio-emotional processing to parenting specific behavior: a study of mothers with and without posttraumatic stress disorder

Socio-emotional information processing during everyday human interactions has been assumed to translate to social-emotional information processing when parenting a child. Yet, few studies have examined whether this is indeed the case. This study aimed to improve on this by connecting the functional neuroimaging data when seeing socio-emotional interactions that are not parenting specific to observed maternal sensitivity. The current study considered 45 mothers of small children (12–42 months of age). It included healthy controls (HC) and mothers with interpersonal violence-related posttraumatic stress disorder (IPV-PTSD), as well as mothers without PTSD, both with and without IPV exposure. We found that anterior cingulate cortex (ACC) and ventromedial prefrontal cortex (vmPFC) activity correlated negatively with observed maternal sensitivity when mothers watched videos of menacing vs. prosocial adult male–female interactions. This relationship was independent of whether mothers were HC or had IPV-PTSD. We also found dorsolateral prefrontal cortex (dlPFC) activity to be correlated negatively with maternal sensitivity when mothers watched any kind of arousing adult interactions. With regards to ACC and vmPFC activity, we interpret our results to mean that the ease of general emotional information integration translates to parenting-specific behavior. Our dlPFC activity findings support the idea that the efficiency of top-down control of socio-emotional processing in non-parenting specific contexts may be predictive of parenting behavior.

Factors associated with antenatal depression and obstetric complications in immigrant women in Geneva

OBJECTIVE immigrant women are at increased risk for health problems during pregnancy, and for antenatal and postnatal depression. This study aimed to identify sociodemographic and specific psychosocial risk factors of antenatal depression and obstetric complications in an economically and culturally heterogeneous sample. DESIGN prospective cross-sectional design. SETTING the study was conducted in a midwifery office. PARTICIPANTS the community sample included 228 immigrant pregnant women with low French proficiency referred to birth preparation classes between 2006 and 2014 in Geneva, Switzerland. MEASUREMENT depressive symptoms were measured during the third trimester of pregnancy using the Edinburgh Postnatal Depression Scale. A cut-off score ≥12 was considered to be indicative of antenatal depression. FINDINGS more than half of the participants had been living in Switzerland for less than five years and had a short-term residence permit. Thirty-seven per cent of women scored above the clinical cut-off score. Women with several risk factors, such as a precarious legal status, lack of marital support, difficult living conditions and being a newcomer to Switzerland, were at higher risk of depression. Women who encountered difficult living conditions were at higher risk of obstetric complications. IMPLICATIONS FOR PRACTICE these results confirm the findings of previous research, and highlight the need for early detection. Public health prevention policies should consist of multidimensional programmes to address simultaneously psychosocial, cultural and obstetric issues in pregnant immigrant women.

Maternal PTSD and corresponding neural activity mediate effects of child exposure to violence on child PTSD symptoms

The aim of this study was to examine the relationship of maternal interpersonal violence-related posttraumatic stress disorder (IPV-PTSD), associated neural activity in response to mother-child relational stimuli, and child psychopathology indicators at child ages 12–42 months and one year later. The study tested the hypothesis that decreased maternal neural activity in regions that subserve emotion regulation would be associated with child symptoms associated with emotional dysregulation at both time points. Functional magnetic resonance imaging of 42 mothers with or without violence-exposure and associated IPV-PTSD were assessed. Their child’s life-events and symptoms/behaviors indicative of high-risk subsequent PTSD diagnosis on a maternal-report questionnaire were measured one year later. Maternal IPV-PTSD severity was significantly associated with decreased ventromedial prefrontal cortex (vmPFC) activation in response to mother-child relational stimuli. Maternal IPV-PTSD severity and decreased vmPFC activation were then significantly associated with a child attachment disturbance at 12–42 months and symptoms/behaviors one year later, that were correlated with emotional dysregulation and risk for child PTSD. Maternal IPV-PTSD and child exposure to IPV were both predictive of child PTSD symptoms with maternal IPV-PTSD likely mediating the effects of child IPV exposure on child PTSD symptoms. These findings suggest that maternal IPV-PTSD severity and associated decreased vmPFC activity in response to mother-child relational stimuli are predictors of child psychopathology by age 12–42 months and one-year later. Significant findings in this paper may well be useful in understanding how maternal top-down cortico-limbic dysregulation promotes intergenerational transmission of IPV and related psychopathology and, thus should be targeted in treatment.

Trauma and Parenting: Informing Clinical Practice with Recent Research Findings

Opinion statementPost-traumatic stress disorder (PTSD) is a common consequence of interpersonal violence (IPV). Maternal IPV-related PTSD has been shown to interfere with the mothers’ ability to join with their children in mutual emotion regulation, a pre-requisite for the development of self-regulation. Studies have shown that parental reflective functioning (PRF; i.e., the attribution of mental states that may be inferred to motivate interactive behavior) and maternal sensitivity (MS) are protective factors. Both PRF and MS are associated with secure child-parent attachment. The stronger these factors are at baseline, the more they improve the chances of a mother with IPV-PTSD seeking help in order to benefit quickly from both physical and mental health assessment and intervention. Pediatricians should routinely assess the history of IPV in the family environment taking into account the parent-child relationship, through observing parent-child interaction and listening to how the parent talks about her child and other important attachment relationships. Health professionals can learn to support and model PRF with traumatized parents.

Maternal Trauma and Related Psychopathology: Consequences to Parental Brain Functioning Associated with Caregiving

The chapter takes as its departure point the Winnicottian notion of “Good-enough mothering” as being tied to the capacity of the primary caregiver to engage in mutual emotion regulation during sensitive periods of early development. Maternal experience of interpersonal violence and related psychopathology (i.e. posttraumatic stress disorder) through associated emotional dysregulation and activation of traumatic memory traces even by routine mother–infant interactions (i.e. interactions such as separations involving child helplessness) perturbs this mutual regulation. Original research from the Geneva Early Childhood Stress Project is described to support that both neural activity and epigenetics of stress-linked genes are promising as (1) important markers of these hypothesized mechanisms and (2) useful measures of the effectiveness of targeted parent–child interventions. The role of individual differences played by possible endophenotypes in the intergenerational transmission of trauma and associated psychopathology, as for example that noted for mothers with prominent dissociative symptoms, is discussed with its clinical implications.