Dataset Information

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.

SUBMITTER: Stonawski V

PROVIDER: S-EPMC7298426 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Stonawski Valeska V Roetner Jakob J Goecke Tamme W TW Fasching Peter A PA Beckmann Matthias W MW Kornhuber Johannes J Kratz Oliver O Moll Gunther H GH Eichler Anna A Heinrich Hartmut H Frey Stefan S

Epigenetics insights 20200616

<h4>Background</h4>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.<h4>Methods</h4>In an epigenome-wide association study (EWAS), alterations of DNA methylat ...[more]

PMID: 32596638

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Project description:BackgroundPrenatal 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.ResultsNo 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.ConclusionAlthough 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.

Project description:Older adults are more susceptible to higher inflammatory levels and depression. Moreover, diet may influence inflammation as well as depression but no previous study examined whether inflammatory dietary patterns are related to depression in an older population. To investigate the longitudinal association between inflammatory dietary patterns (using reduced rank regression (RRR)) and depressive symptoms in a population sample of Italian older adults.We included 827 participants (aged?65years) at baseline in 1998. Follow-up measurements were collected after 3, 6 and 9years. We used RRR to identify inflammatory dietary patterns at baseline. The Centre for Epidemiologic Studies Depression (CES-D) scale was used to assess depressive symptoms by using continuous scores and depression by using a cut-off point (CES-D?20).We identified two inflammatory dietary patterns using different sets of response variables. Dietary pattern I was related to inflammatory markers C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor ? and was characterized by high intakes of refined grains, sweet snacks, pasta and rice. After full adjustment for confounders, no longitudinal association was found when comparing extreme quartiles of this dietary pattern and depressive symptoms (Q1vs Q4, model 4: B=0.04, 95% CI: -0.06, 0.13) or depression (Q1vs Q4, model 4: OR=0.90, 95% CI: 0.55, 1.45). Dietary pattern II was related to inflammatory markers CRP, IL-18, IL-1?, IL-1 receptor antagonist and was characterized by high intakes of pasta, sugar-sweetened beverages, processed meat and chocolate and sweets. When comparing extreme quartiles, this dietary pattern was not longitudinally associated with depressive symptoms (Q1vs Q4, model 4: B=-0.04, 95% CI: -0.13, 0.05) but an inverse association was found for depression (Q1vs Q4, model 4: OR=0.56, 95% CI: 0.40, 0.94).Our study does not support the hypothesis that dietary patterns linked to inflammatory markers are associated with higher depressive symptoms and higher depression incidence. However, dietary intake in our population of older adults was quite homogeneous which makes it difficult to show clear associations.

Project description:BACKGROUND:Perinatal depressive symptoms have been linked to adverse maternal and infant health outcomes. The etiology associated with perinatal depressive psychopathology is poorly understood, but accumulating evidence suggests that understanding inter-individual differences in DNA methylation (DNAm) patterning may provide insight regarding the genomic regions salient to the risk liability of perinatal depressive psychopathology. RESULTS:Genome-wide DNAm was measured in maternal peripheral blood using the Infinium MethylationEPIC microarray. Ninety-two participants (46% African-American) had DNAm samples that passed all quality control metrics, and all participants were within 7 months of delivery. Linear models were constructed to identify differentially methylated sites and regions, and permutation testing was utilized to assess significance. Differentially methylated regions (DMRs) were defined as genomic regions of consistent DNAm change with at least two probes within 1?kb of each other. Maternal age, current smoking status, estimated cell-type proportions, ancestry-relevant principal components, days since delivery, and chip position served as covariates to adjust for technical and biological factors. Current postpartum depressive symptoms were measured using the Edinburgh Postnatal Depression Scale. Ninety-eight DMRs were significant (false discovery rate < 5%) and overlapped 92 genes. Three of the regions overlap loci from the latest Psychiatric Genomics Consortium meta-analysis of depression. CONCLUSIONS:Many of the genes identified in this analysis corroborate previous allelic, transcriptomic, and DNAm association results related to depressive phenotypes. Future work should integrate data from multi-omic platforms to understand the functional relevance of these DMRs and refine DNAm association results by limiting phenotypic heterogeneity and clarifying if DNAm differences relate to the timing of onset, severity, duration of perinatal mental health outcomes of the current pregnancy or to previous history of depressive psychopathology.

Dataset Information

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

Publications

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

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