FKBP5 Moderates the Association between Antenatal Maternal Depressive Symptoms and Neonatal Brain Morphology

Abstract

Antenatal maternal depressive symptoms influence fetal brain development and increase the risk for depression in offspring. Such vulnerability is often moderated by the offspring's genetic variants. This study aimed to examine whether FKBP5, a key regulator of the hypothalamic-pituitary-adrenal (HPA) axis, moderates the association between antenatal maternal depressive symptoms and in utero brain development, using an Asian cohort with 161 mother-offspring dyads. Antenatal maternal depressive symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS) during the second trimester of pregnancy. Neonatal structural brain images were acquired using magnetic resonance imaging (MRI) shortly after birth. Maternal and neonatal FKBP5 gene was genotyped using Illumina OmniExpress arrays. A gene set-based mixed effect model for gene-environment interaction (MixGE) was used to examine interactive effects between neonatal genetic variants of FKBP5 and antenatal maternal depressive symptoms on neonatal amygdala and hippocampal volumes, and cortical thickness. Our study revealed that genetic variants in neonatal FKBP5 moderate the association between antenatal maternal depressive symptoms and right hippocampal volume but only show a trend for such moderation on amygdala volumes and cortical thickness. Our findings are the first to reveal that the association between maternal depressive symptoms and in utero neurodevelopment of specific brain regions is modified through complex genetic variation in neonatal FKBP5. Our results suggest that an increased risk for depression may be transmitted from mother to child during fetal life and that the effect is dependent upon neonatal FKBP5 genotype.