Genome-Wide DNA Methylation Patterns in Children Exposed to Nonpharmacologically Treated Prenatal Depressive Symptoms: Results From 2 Independent Cohorts

Abstract

Background: Maternal depressive symptoms are a common phenomenon during pregnancy and are related to negative outcomes for child development and health. Modifications in child DNA methylation are discussed as an underlying mechanism for the association between prenatal depressive symptoms and alterations in child outcomes. However, formerly reported genome-wide associations have yet to be replicated. Methods: In an epigenome-wide association study (EWAS), alterations of DNA methylation related to maternal prenatal depressive symptoms were investigated in buccal cell samples from 174 children (n = 52 exposed to prenatal depressive symptoms; 6-9 years old) of the German longitudinal study FRAMES-FRANCES. Whole blood samples from the independent, age-comparable ARIES subsample of the ARIES/ALSPAC study (n = 641; n = 159 exposed to prenatal depressive symptoms; 7-8 years old) were examined as a confirmation sample. Depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale. DNA methylation was analyzed with the Infinium Human Methylation 450k BeadChip. Modifications in single CpGs, regions, and biological pathways were investigated. Results were adjusted for age and birth outcomes as well as postnatal and current maternal depressive symptoms. Analyses were performed for the whole sample as well as separated for sex. Results: The EWAS yielded no differentially methylated CpG or region as well as no accordance between samples withstanding correction for multiple testing. In pathway analyses, no overlapping functional domain was found to be enriched for either sample. A comparison of current and former findings suggests some overlapping methylation modifications from infancy to childhood. Results suggest that there might be sex-specific differential methylation, which should be further investigated in additional studies. Conclusions: The current, mainly nonsignificant, results challenge the assumption of consistent modifications of DNA methylation in children exposed to prenatal depressive symptoms. Despite the relatively small sample size used in this study, this lack of significant results may reflect diverse issues of environmental epigenetic studies, which need to be addressed in future research.

Epigenome-wide association studies of prenatal maternal mental health and infant epigenetic profiles: a systematic review

“…We found that no replicated single significant CpG sites were reported from more than one study in any of the three categories (maternal depression, maternal depression treatment, and maternal anxiety). However, one CpG site, cg25157095 was found among the top non-significant CpG sites for maternal depression in two studies [40,47]. This CpG site is in an intron for the RIPK4 gene which has been implicated in keratinocyte differentiation, modulation of the actin cytoskeleton, and restricting intercellular adhesion [51].…”

“…2). Several articles described analyses of more than one exposure, resulting in 16 analyses [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47] of maternal depression, 8 analyses [32,35,38,39,44,45,47,48] of maternal depression treatment, and 9 analyses [27,32,33,35,38,41,47,49,50] of maternal anxiety (Table S1). Based on STROBE and ROBINS-I criteria, we found that 13 analyses had a moderate risk of bias and 7 had a severe risk of bias (Tables S2 and S3).…”

Salud mental intergeneracional

“…Pero en algún estudio más reciente no se han hallado efectos significativos de la exposición Rev Neuropsiquiatr. 2023;86(1): [35][36][37][38][39][40][41][42][43][44] al estrés experimentado por la madre en la metilación neonatal de la sangre del cordón umbilical uterino (22) y se ha llegado a desafiar la hipótesis de que sucedan modificaciones consistentes de la metilación del ADN en niños expuestos a síntomas depresivos maternos prenatales (23).…”

Periconception and Prenatal Exposure to Maternal Perceived Stress and Cord Blood DNA Methylation

“…12 , 16 More recently, EWAS studies have been conducted to examine prenatal depressive symptoms or stressful life events; however, these studies have not replicated the findings of candidate gene studies. 17 - 20 …”