DNA methylation in cord blood in association with prenatal depressive symptoms

Abstract

Background Prenatal symptoms of depression (PND) and anxiety affect up to every third pregnancy. Children of mothers with mental health problems are at higher risk of developmental problems, possibly through epigenetic mechanisms together with other factors such as genetic and environmental. We investigated DNA methylation in cord blood in relation to PND, taking into consideration a history of depression, co-morbidity with anxiety and selective serotonin reuptake inhibitors (SSRI) use, and stratified by sex of the child. Mothers (N = 373) prospectively filled out web-based questionnaires regarding mood symptoms and SSRI use throughout pregnancy. Cord blood was collected at birth and DNA methylation was measured using Illumina MethylationEPIC array at 850 000 CpG sites throughout the genome. Differentially methylated regions were identified using Kruskal–Wallis test, and Benjamini-Hochberg adjusted p-values < 0.05 were considered significant. Results No differential DNA methylation was associated with PND alone; however, differential DNA methylation was observed in children exposed to comorbid PND with anxiety symptoms compared with healthy controls in ABCF1 (log twofold change − 0.2), but not after stratification by sex of the child. DNA methylation in children exposed to PND without SSRI treatment and healthy controls both differed in comparison with SSRI exposed children at several sites and regions, among which hypomethylation was observed in CpGs in the promoter region of CRBN (log2 fold change − 0.57), involved in brain development, and hypermethylation in MDFIC (log2 fold change 0.45), associated with the glucocorticoid stress response. Conclusion Although it is not possible to assess if these methylation differences are due to SSRI treatment itself or to more severe depression, our findings add on to existing knowledge that there might be different biological consequences for the child depending on whether maternal PND was treated with SSRIs or not.

Profiling placental DNA methylation associated with maternal SSRI treatment during pregnancy

“…In a different cohort, Kallak et al reported 13 CpGs differentially methylated by SSRI exposure status in cord blood 69 . Though cord blood DNAme is very distinct from placenta, we sought to evaluate whether any of the 14 CpGs reported by Cardenas et al 68 or Kallak et al 69 were also differentially methylated by SSRI exposure status in the placenta. At the CpG reported by Cardenas et al (cg22159528) we found no difference in DNAme by SSRI exposure (nominal p value > 0.05), see Fig.…”

“…At one of the 13 CpGs reported by Kallak et al, we found nominally significant ( p < 0.05) differential DNAme associated with SSRI exposure status in the placenta in the same direction as the original cord blood association: higher DNAme in SSRI-exposed cases. This was cg00331486 in LOC284930 on chromosome 22, which encodes a MYC-interacting long noncoding RNA species 69 .…”

Maternal–fetal stress and DNA methylation signatures in neonatal saliva: an epigenome-wide association study

“…Previous studies employing EPIC array on neonatal tissues in association with maternal stress and/or anxiety are limited to one study by Kallak et al [ 75 ]. These authors investigated DNA methylation in cord blood of newborns exposed to maternal depression and anxiety.…”

The role of DNA methylation in progression of neurological disorders and neurodegenerative diseases as well as the prospect of using DNA methylation inhibitors as therapeutic agents for such disorders

“…One of the main neurobiological mechanisms of depression is dysregulated and dysfunctional stress response system (such as hypothalamic-pituitary-adrenal (HPA) axis activity and glucocorticoid receptor (GR) sensitivity) to show the adaptive change ( Guo et al, 2021 ). Moreover, prenatal depressive symptoms might influence fetal epigenetic programming ( Kallak et al, 2021 ). Prenatal depression is associated with differential methylation in GNAS, CTNNA2, OSBPL10, and 5-HTTLPR ( Sales et al, 2021 , Drzymalla et al, 2021 ).…”