Sandra Rusconi Serpa

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.

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.

Negative and Distorted Attributions Towards Child, Self, and Primary Attachment Figure Among Posttraumatically Stressed Mothers: What Changes with Clinician Assisted Videofeedback Exposure Sessions (CAVES)

Abstract This study found that within a non-referred community pediatrics clinic sample, the severity of mothers’ trauma-related psychopathology, in particular, their interpersonal violence-related (IPV) posttraumatic stress, dissociative, and depressive symptoms predicted the degree of negativity of mothers’ attributions towards their preschool age children, themselves, and their own primary attachment figure. Results also showed that mothers with IPV-related posttraumatic stress disorder (PTSD) as compared to non-PTSD controls showed a significantly greater degree of negativity of their attributions toward their child, themselves and their primary attachment figure during childhood. The study finally found a significant reduction in the degree of negativity of mothers’ attributions only towards their child following a three-session evaluation-protocol that included a form of experimental intervention entitled the “Clinician Assisted Videofeedback Exposure Session(s)” (CAVES), for mothers with IPV-PTSD as compared to control-subjects.

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.

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.

The Association of Maternal Exposure to Domestic Violence During Childhood With Prenatal Attachment, Maternal-Fetal Heart Rate, and Infant Behavioral Regulation

Human and animal models suggest that maternal hormonal and physiological adaptations during pregnancy shape maternal brain functioning and behavior crucial for offspring care and survival. Less sensitive maternal behavior, often associated with psychobiological dysregulation and the offsprings behavioral and emotional disorders, has been observed in mothers who have experienced adverse childhood experiences. Strong evidence shows that children who are exposed to domestic violence (DV) are at risk of being abused or becoming abusive in adulthood. Yet little is known about the effect of childhood exposure to DV on the expecting mother, her subsequent caregiving behavior and related effects on her infant. Thus, the present study examined the association of maternal exposure to DV during childhood on prenatal maternal attachment, maternal heart rate reactivity to an infant-crying stimulus and post-natal infant emotional regulation. Thirty-three women with and without exposure to DV during childhood were recruited during the first trimester of pregnancy and followed until 6-month after birth. The Maternal Antenatal Attachment Scale (MAAS) was used to measure prenatal attachment of the mother to her fetus during the second trimester of pregnancy, maternal and fetal heart rate reactivity to an infant-crying stimulus was assessed at the third trimester of pregnancy, and the Infant Behavior Questionnaire-Revised (IBQ-R) was used to assess infant emotional regulation at 6-months. Results showed that pregnant women that were exposed to DV during childhood had a poorer quality of prenatal attachment of mother to fetus, regardless of whether they also experienced DV during adulthood. In addition, maternal exposure to DV during childhood was associated with increased maternal heart rate to infant-crying stimulus and worse infant emotional regulation. These findings highlight the importance of prenatal screening for maternal exposure to DV during childhood as a risk factor for disturbances in the development of maternal attachment, dysfunctional maternal behavior and emotion dysregulation.

Intergenerational Transmission of DNA Methylation Signatures Associated with Early Life Stress

Early life stress in humans (i.e. maltreatment, violence exposure, loss of a loved one) and in rodents (i.e. disrupted attachment or nesting, electric shock, restraint, predator odor) occurs during critical steps of neural circuit formation. ELS in humans is associated with increased risk for developmental psychopathology, including anxious and depressive phenotypes. The biological mechanisms underlying these potentially persistent maladaptive changes involve long-term epigenetic modifications, which have been suggested to be potentially transmissible to subsequent generations. DNA methylation is an epigenetic mechanism that modifies gene expression patterns in response to environmental challenges and influences mutation rates. It remains to be seen whether a functionally relevant fraction of DNA methylation marks can escape genome-wide erasures that occur in primordial germ cells and after fertilization within the zygote. Early life-stress-triggered changes in epigenetic mediated transmission of acquired behavioral traits among humans have been assessed mainly by targeting genes involved in the hypothalamic-pituitary-adrenal (HPA) axis, such as NR3C1 and FKBP5. Recently, researchers examining epigenetic transmission have begun to apply genome-wide approaches. In humans, reduced representation bisulfite sequencing (RRBS) was performed on peripheral samples that were obtained from individuals who were prenatally exposed to the “Dutch Hunger Winter”, resulting in two Differentially Methylated Regions (DMRs) in INSR and CPTIA genes that were functionally, biologically and technically validated, and significantly associated with birth weights and LDL cholesterol levels in offspring. In rodents, non-genomic intergenerational transmission of anxiety which was associated with differentially methylated enhancers that were putatively involved in lipid signaling and synaptic/neurotransmission in hippocampal granule cells, was discovered also using RRBS. Finally, transgenerational transmission of altered behaviors was associated with sperm-derived microRNAs produced by ELS male mice. The field of epigenetic transmission is just beginning to enter the epigenomic era by using genome-wide analyses. Such approaches remain of strong interest to human studies, first in order to help to assess the relevance of the previous targeted studies, and second to discover new important epigenetic modifications of potential clinical importance. New discoveries may help to assess how transmittable the negative impact of stress may be to offspring. The latter may open doors for future treatments and resilience-promoting interventions, as well as new approaches to treat the effects of childhood trauma before the onset of psychiatric disorder.