Maternal Childhood Maltreatment-Influenced Prenatal Programming of Early Brain-Behavior and Risk for Future Psychopathology

PROJECT SUMMARY The proposed research aims will provide support for a novel pathway of intergenerational trauma through new- born amygdala network connectivity programmed in utero influencing infant emotion regulation problems that may lead to less optimal mother-infant interactions (e.g., disorganized attachment), resulting in increased risk for psychopathology. The proposed training will add to the applicants’ background in perinatal psychology and developmental psychopathology to include needed training in newborn brain imaging and enable their future independent career as a clinician-scientist with expertise in novel pathways of intergenerational trauma through in utero programming of early brain-behavior leading to increased risk for psychopathology, informing critical malleable windows for early intervention. In one study, 40% of children developed anxiety disorders when their mother experienced childhood maltreatment (MCM), as compared to only 24% in the absence of MCM. Most known pathways of transmission are behavioral, with limited evidence for biological transmission. Well-estab- lished behavioral pathways are through maternal psychological state and parenting sensitivity influencing infant emotion regulation and mother-infant attachment. Emerging evidence supports MCM effects on infant out- comes through biological pathways such as in utero programming of brain development, e.g., MCM was asso- ciated with greater newborn resting-state functional connectivity (rsFC) between the amygdala and regions of the prefrontal cortex (PFC) and key brain networks implicated in stress processing. However, associations be- tween MCM-influenced alterations in amygdala network connectivity with infant behavior or child outcomes have yet to be established, limiting the clinical application of emergent literature. The candidate will address a critical gap in the literature by investigating a novel biological pathway of intergenerational trauma: MCM-influ- enced prenatal programming shaping newborn amygdala network connectivity prior to postnatal influences (i.e., substantiating prenatal programming of MCM transmission), in association with infant emotion regulation problems (i.e., making emergent research more clinically relevant), resulting in increased risk for psychopathol- ogy. Mediators and moderators will also be considered, such as maternal prenatal psychological state, psycho- social health, health behaviors, social determinants of health, infant health, and infant biological sex. The appli- cant will obtain training in newborn functional magnetic resonance imaging (fMRI), laboratory observational assessment of infant behavior, theory and science of intergenerational trauma, and biostatistics. The K99/R00 will inform the candidate’s first R01 proposal with specific hypotheses about brain circuits associated with in- fant emotion regulation problems and disorganized attachment as RDoC informed indicators of future risk for child psychopathology, and guide decisions for obtaining subsequent fMRI and interdisciplinary longitudinal multi-level assessment. Future R01s will build a research program to investigate novel pathways of intergener- ational trauma through early brain-behavior programmed in utero leading to changes in infant and child social- emotional development and family dynamics, with mediators and moderators prior to and throughout preg- nancy, to help mitigate risk for intergenerational transmission of trauma and psychopathology. The K99/R00 will culminate in a successful transition to career independence.