Background:Methylation ofthe serotonin 3Areceptor gene (HTR3A) has been linked to childmaltreatment
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.