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FKBP5 Moderates the Association between Antenatal Maternal Depressive Symptoms and Neonatal Brain Morphology
Changqing Wang1, Mojun Shen2, Bryan Guillaume1
1Department of Biomedical Engineering and Clinical Imaging Research Center, National University of Singapore, Singapore.
Insights
Maternal depression during pregnancy affects fetal brain development. Neonatal FKBP5 gene variants moderate this association, specifically impacting right hippocampal volume in offspring, suggesting a genetically influenced transmission of depression risk.
Area of Science:
- Neuroscience
- Genetics
- Psychiatry
Background:
- Antenatal maternal depressive symptoms negatively impact fetal brain development.
- Offspring genetic variants can moderate the vulnerability to maternal depression.
- FKBP5 is a key regulator of the hypothalamic-pituitary-adrenal (HPA) axis, implicated in stress response and depression.
Purpose of the Study:
- To investigate if neonatal FKBP5 gene variants moderate the association between antenatal maternal depressive symptoms and in utero brain development.
- To analyze the impact on neonatal amygdala and hippocampal volumes and cortical thickness.
Main Methods:
- Study cohort: 161 Asian mother-offspring dyads.
- Maternal depressive symptoms assessed using Edinburgh Postnatal Depression Scale (EPDS) in the second trimester.
- Neonatal brain structure analyzed via MRI; FKBP5 gene genotyped.
- Gene-environment interaction examined using a gene set-based mixed effect model (MixGE).
Main Results:
- Neonatal FKBP5 genetic variants significantly moderated the link between antenatal maternal depressive symptoms and right hippocampal volume.
- A trend for moderation was observed for amygdala volumes and cortical thickness.
- This is the first study to demonstrate FKBP5's role in modifying maternal depression's impact on fetal neurodevelopment.
Conclusions:
- Neonatal FKBP5 genotype influences how antenatal maternal depressive symptoms affect fetal brain development, particularly hippocampal volume.
- Findings suggest a potential pathway for transmitting depression risk from mother to child via fetal development, modulated by neonatal genetics.
- This highlights the complex interplay between maternal mental health, fetal neurodevelopment, and genetic factors.
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.
