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.

产前抑郁症很常见，认识不足，治疗不足。它对孩子的行为和大脑发育有负面影响，但产前抑郁，孩子的行为和孩子的大脑结构之间的关系仍然不清楚。这项研究的目的是确定改变大脑的连通性是否介导产前产妇抑郁症状与儿童行为之间的关系。这项研究包括54对人类母子对。母亲在妊娠中期和中期以及产后三个月完成了爱丁堡产后抑郁量表。他们的孩子在4.1±0.8岁时进行了MRI扩散检查，并在MRI扫描后的6个月内使用“儿童行为清单”对孩子的行为进行了评估。杏仁核，穹隆，束状筋膜，使用分数各向异性和平均扩散率评估扣带，并分析产妇的产前抑郁症状以及儿童行为。孕晚期孕妇的爱丁堡产后抑郁量表得分与杏仁核-额叶和扣带的平均扩散率呈正相关，控制了产后抑郁。外在行为在杏仁核-额叶途径中具有性别相互作用。较弱的连通性（较低的分数各向异性，较高的平均扩散率）与男孩的不良行为有关。杏仁核与额叶的连接介导了男性的晚期妊娠抑郁症状与儿童外在行为之间的关系。这些发现表明，大脑结构的改变是一种机制，通过这种机制，产前抑郁症状会影响儿童的行为，

重要性声明了解产前产妇抑郁如何影响儿童行为对于正确治疗产前产妇心理健康问题和改善儿童结局至关重要。在这里，我们显示了暴露于产前产前抑郁症状的幼儿中的白质变化。抑郁症状加重的母亲的孩子在与情感加工有关的区域之间的白质连通性较弱。此外，杏仁核和前额叶皮层之间的连通性介导了男孩的母亲抑郁症状和外在行为之间的关系，表明大脑结构的改变是母亲产前抑郁症影响儿童行为的可能机制。