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.

Keywords: CBCL; Cord blood; DNA methylation; EPDS; EWAS; Prenatal depressive symptoms; Women.

Fig. 1

Flowchart describing selection of mothers for DNA methylation analysis from the BASIC study cohort

Fig. 2

Venn diagram displaying genes with CpGs differently methylated in cord blood from children with mothers experiencing prenatal depressive symptoms (PND) without selective serotonin receptor inhibitor (SSRI) treatment compared with PND with SSRI treatment (blue) and healthy controls compared with PND with SSRI treatment (grey). Arrow pointing upwards indicates higher DNA methylation in the PND without SSRI group (blue) or HC (grey) in comparison with PND with SSRI treatment while arrows pointing downwards indicate lower DNA methylation