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Exploring the effect of antenatal depression treatment on children's epigenetic profiles: findings from a pilot
Laura S Bleker1,2, Jeannette Milgrom3,4, Alexandra Sexton-Oates5
1Department of Obstetrics and Gynecology, Amsterdam UMC, location AMC, Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands. l.s.bleker@amc.uva.nl.
Insights
Maternal cognitive behavioral therapy (CBT) during pregnancy may influence children's DNA methylation patterns. This study found preliminary evidence of widespread methylation changes in children exposed to CBT, though further research is needed.
Area of Science:
- Epigenetics
- Developmental Psychology
- Perinatal Mental Health
Background:
- Maternal depression during pregnancy is linked to behavioral and emotional problems in children, potentially via epigenetic alterations.
- Existing evidence primarily comes from animal and observational human studies.
- Experimental human studies are needed to confirm the impact of prenatal interventions on child epigenetics.
Purpose of the Study:
- To investigate the effects of cognitive behavioral therapy (CBT) for antenatal depression on children's DNA methylation.
- To compare genome-wide DNA methylation in children whose mothers received CBT versus treatment as usual (TAU) during pregnancy.
- To explore associations between maternal depression severity and offspring DNA methylation.
Main Methods:
- Follow-up of a randomized controlled trial (RCT) comparing CBT and TAU for antenatal depression.
- Analysis of DNA methylation in buccal swabs from children aged 3-7 years (N=23).
- Genome-wide methylation analysis at 770,668 CpG sites and targeted analysis of 729 CpG sites in candidate genes, including NR3C1.
Main Results:
- Children of mothers who received CBT showed generally lower DNA methylation compared to the TAU group (mean ∆β = -0.028).
- A trend towards lower methylation was observed at a specific CpG site (cg26464411) in the NR3C1 gene in the CBT group.
- No significant differences in DNA methylation were found between groups after correction for multiple testing, nor were associations found with maternal depression severity.
Conclusions:
- Preliminary evidence suggests a potential effect of maternal CBT on widespread DNA methylation in children.
- A trend towards altered methylation at a specific gene (NR3C1) was noted but did not reach statistical significance.
- Larger studies are warranted to confirm these findings and understand the long-term implications of prenatal interventions on child epigenetics.
Background:
Children prenatally exposed to maternal depression more often show behavioral and emotional problems compared to unexposed children, possibly through epigenetic alterations. Current evidence is largely based on animal and observational human studies. Therefore, evidence from experimental human studies is needed. In this follow-up of a small randomized controlled trial (RCT), DNA-methylation was compared between children of women who had received cognitive behavioral therapy (CBT) for antenatal depression and children of women who had received treatment as usual (TAU). Originally, 54 women were allocated to CBT or TAU. A beneficial treatment effect was found on women's mood symptoms.
Findings:
We describe DNA methylation findings in buccal swab DNA of the 3-7-year-old children (CBT(N) = 12, TAU(N) = 11), at a genome-wide level at 770,668 CpG sites and at 729 CpG sites spanning 16 a priori selected candidate genes, including the glucocorticoid receptor (NR3C1). We additionally explored associations with women's baseline depression and anxiety symptoms and offspring DNA methylation, regardless of treatment. Children from the CBT group had overall lower DNA methylation compared to children from the TAU group (mean ∆β = - 0.028, 95% CI - 0.035 to - 0.022). Although 68% of the promoter-associated NR3C1 probes were less methylated in the CBT group, with cg26464411 as top most differentially methylated CpG site (p = 0.038), mean DNA methylation of all NR3C1 promoter-associated probes did not differ significantly between the CBT and TAU groups (mean ∆β = 0.002, 95%CI - 0.010 to 0.011). None of the effects survived correction for multiple testing. There were no differences in mean DNA methylation between the children born to women with more severe depression or anxiety compared to children born to women with mild symptoms of depression or anxiety at baseline (mean ∆β (depression) = 0.0008, 95% CI - 0.007 to 0.008; mean ∆β (anxiety) = 0.0002, 95% CI - 0.004 to 0.005).
Conclusion:
We found preliminary evidence of a possible effect of CBT during pregnancy on widespread methylation in children's genomes and a trend toward lower methylation of a CpG site previously shown by others to be linked to depression and child maltreatment. However, none of the effects survived correction for multiple testing and larger studies are warranted.
Trial Registration:
Trial registration of the original RCT: ACTRN12607000397415 . Registered on 2 August 2007.
