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Prenatal depression is common, underrecognized, and undertreated. It has negative consequences on child behavior and brain development, yet the relationships among prenatal depression, child behavior, and children's brain structure remain unclear. The aim of this study was to determine whether altered brain connectivity mediates relationships between prenatal maternal depressive symptoms and child behavior. This study included 54 human mother-child pairs. Mothers completed the Edinburgh Postnatal Depression Scale during the second and third trimesters of pregnancy and 3 months postpartum. Their children had diffusion MRI at age 4.1 ± 0.8 years, and children's behavior was assessed using the Child Behavior Checklist within 6 months of their MRI scan. Structural brain connectivity of the amygdala, fornix, uncinate fasciculus, and cingulum was assessed using fractional anisotropy and mean diffusivity and analyzed with maternal prenatal depressive symptoms as well as child behavior. Third trimester maternal Edinburgh Postnatal Depression Scale scores were positively associated with mean diffusivity in the amygdala-frontal tract and the cingulum, controlling for postpartum depression. Externalizing behavior had a sex interaction in the amygdala-frontal pathway; weaker connectivity (lower fractional anisotropy, higher mean diffusivity) was associated with worse behavior in boys. Amygdala-frontal connectivity mediated the relationship between third trimester depressive symptoms and child externalizing behavior in males. These findings suggest that altered brain structure is a mechanism via which prenatal depressive symptoms can impact child behavior, highlighting the importance of both recognition and intervention in prenatal depression. SIGNIFICANCE STATEMENT Understanding how prenatal maternal depression impacts child behavior is critical for appropriately treating prenatal maternal mental health problems and improving child outcomes. Here, we show white matter changes in young children exposed to maternal prenatal depressive symptoms. Children of mothers with worse depressive symptoms had weaker white matter connectivity between areas related to emotional processing. Furthermore, connectivity between the amygdala and prefrontal cortex mediated the relationship between maternal depressive symptoms and externalizing behavior in boys, showing that altered brain structure is a possible mechanism via which maternal prenatal depression impacts children's behavior. This provides important information for understanding why children of depressed mothers may be more vulnerable to depression themselves and may help shape future guidelines on maternal prenatal care.

Amygdala-Prefrontal Structural Connectivity Mediates the Relationship between Prenatal Depression and Behavior in Preschool Boys