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DNA methylation associated with postpartum depressive symptoms overlaps findings from a genome-wide association meta-analysis of depression.

ABSTRACT: 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.

SUBMITTER: Lapato DM

PROVIDER: S-EPMC6883636 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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DNA methylation associated with postpartum depressive symptoms overlaps findings from a genome-wide association meta-analysis of depression.

Lapato Dana M DM Roberson-Nay Roxann R Kirkpatrick Robert M RM Webb Bradley T BT York Timothy P TP Kinser Patricia A PA

Clinical epigenetics 20191128 1

<h4>Background</h4>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.<h4>Results</h4>Genome-wide DNAm was measured in maternal ...[more]

PMID: 31779682

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Project description:Aim: Be a Mom is a self-guided, web-based intervention to prevent persistent postpartum depression symptoms [PPD], targeting both at-risk postpartum women and/or women presenting early-onset postpartum depressive symptoms (selective/indicated preventive intervention). Be a Mom is grounded on the principles of Cognitive-Behavior Therapy and incorporates the recent contributions of acceptance and compassion-based approaches (third-wave approaches) applied to the perinatal context. This study aimed to explore the processes underlying therapeutic change in the Be a Mom intervention, by: (1) exploring whether participation in the Be a Mom promotes the enhancement of self-regulatory skills (emotion regulation abilities, psychological flexibility and self-compassion) in comparison with women who did not participate in the program; and (2) exploring whether changes in self-regulatory skills are associated with changes in depressive symptoms, among women who participated in the Be a Mom program. Methods: A pilot randomized, two-arm controlled trial was conducted. Eligible women (presenting PPD risk-factors and/or early-onset PPD symptoms) were enrolled in the study and were randomly assigned to the intervention group (Be a Mom, n = 98) or to the waiting-list control group (n = 96). Participants in both groups completed baseline (T1) and post-intervention assessments (T2), including measures of depressive symptoms, emotion regulation abilities, psychological flexibility and self-compassion. Results: From baseline to post-intervention assessment, women in the intervention group showed a significantly greater decrease in the levels of emotion regulation difficulties (p < 0.001) and a significant greater increase in the levels of self-compassion (p < 0.001) compared to the control group. No significant differences were found concerning psychological flexibility. Moreover, a greater decrease in difficulties in emotion regulation and greater increase in self-compassion levels were significantly associated with a greater decrease in depressive symptoms, among women in the intervention group. Discussion: Be a Mom promotes the enhancement of women's emotion regulation abilities and self-compassion, and this seems to exert a protective effect in the presence of PPD risk factors (or early-onset symptoms) because it led to a reduction of depressive symptoms. By providing some insights into the processes that underlie treatment response to Be a Mom, this study highlights the important role of the targeted third-wave processes applied to the perinatal context.

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:ImportanceDepressive disorders arise from a combination of genetic and environmental risk factors. Epigenetic disruption provides a plausible mechanism through which gene-environment interactions lead to depression. Large-scale, epigenome-wide studies on depression are missing, hampering the identification of potentially modifiable biomarkers.ObjectiveTo identify epigenetic mechanisms underlying depression in middle-aged and elderly persons, using DNA methylation in blood.Design, setting, and participantsTo date, the first cross-ethnic meta-analysis of epigenome-wide association studies (EWAS) within the framework of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium was conducted. The discovery EWAS included 7948 individuals of European origin from 9 population-based cohorts. Participants who were assessed for both depressive symptoms and whole-blood DNA methylation were included in the study. Results of EWAS were pooled using sample-size weighted meta-analysis. Replication of the top epigenetic sites was performed in 3308 individuals of African American and European origin from 2 population-based cohorts.Main outcomes and measuresWhole-blood DNA methylation levels were assayed with Illumina-Infinium Human Methylation 450K BeadChip and depressive symptoms were assessed by questionnaire.ResultsThe discovery cohorts consisted of 7948 individuals (4104 [51.6%] women) with a mean (SD) age of 65.4 (5.8) years. The replication cohort consisted of 3308 individuals (2456 [74.2%] women) with a mean (SD) age of 60.3 (6.4) years. The EWAS identified methylation of 3 CpG sites to be significantly associated with increased depressive symptoms: cg04987734 (P = 1.57 × 10-08; n = 11 256; CDC42BPB gene), cg12325605 (P = 5.24 × 10-09; n = 11 256; ARHGEF3 gene), and an intergenic CpG site cg14023999 (P = 5.99 × 10-08; n = 11 256; chromosome = 15q26.1). The predicted expression of the CDC42BPB gene in the brain (basal ganglia) (effect, 0.14; P = 2.7 × 10-03) and of ARHGEF3 in fibroblasts (effect, -0.48; P = 9.8 × 10-04) was associated with major depression.Conclusions and relevanceThis study identifies 3 methylated sites associated with depressive symptoms. All 3 findings point toward axon guidance as the common disrupted pathway in depression. The findings provide new insights into the molecular mechanisms underlying the complex pathophysiology of depression. Further research is warranted to determine the utility of these findings as biomarkers of depression and evaluate any potential role in the pathophysiology of depression and their downstream clinical effects.

Dataset Information

DNA methylation associated with postpartum depressive symptoms overlaps findings from a genome-wide association meta-analysis of depression.

Publications

DNA methylation associated with postpartum depressive symptoms overlaps findings from a genome-wide association meta-analysis of depression.

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