Maternal stress and depression alter infant DNA, with potential lifelong impact

Researchers uncover how maternal stress and depression can leave a lasting mark on infant DNA, revealing new epigenetic links between mental health and child development.

Study: Association between maternal perinatal stress and depression and infant DNA methylation in the first year of life. Image Credit: Drazen Zigic / Shutterstock

In a recent study published in the journal Translational Psychiatry, researchers investigated associations between maternal perinatal depression and stress and infant DNA methylation (DNAm).

Depression and stress during pregnancy and the first year of the child’s life affect a considerable proportion of mothers. Gestation and the initial years of life are critical and sensitive periods for child development, and stress can affect a child’s developmental trajectory. Maternal depression and stress in pregnancy have been linked to adverse outcomes, including preterm birth and low birth weight.

Mother-infant interactions in the first year of life contribute to the cognitive and behavioral development of the child. Postpartum stress/depression has been associated with delayed cognitive development and behavioral dysfunction. However, the biological pathways linking maternal stress/depression to poor child health outcomes are still largely unknown.

About the Study

In the present study, researchers investigated whether maternal depression and stress are associated with differences in infant DNAm. The Canadian Healthy Infant Longitudinal Development (CHILD) cohort enrolled mothers in their second trimester between 2008 and 2012. Mother-child pairs were followed from birth for up to five years. The primary aim of the CHILD cohort was to identify environmental and genetic determinants of atopic disease.

As such, DNAm samples were selected based on the atopy status of the child. The present study was a secondary analysis involving mother-child pairs from an atopy-enriched subsample with genotype data, epigenome-wide association studies (EWAS), DNAm data from peripheral blood mononuclear cells (PBMCs) and cord blood mononuclear cells (CBMCs), and maternal mental health measures. DNAm was measured in CBMCs at birth and PBMCs at 12 months.

Depression and stress were measured using the Center for Epidemiologic Studies Depression Questionnaire and the Perceived Stress Scale, respectively. Prenatal measures were administered at 18 and 36 weeks during pregnancy, while postnatal measures were administered at six and 12 months postpartum. The two time points were aggregated into a single composite measure for each period.

The study employed robust linear regression models to investigate associations of prenatal and postnatal stress and depression with CBMC and PBMC DNAm. Additionally, bias adjustment techniques, including the bacon and cate methods, were used to control for inflation and unmeasured confounding, which strengthens the reliability of the findings. Four sensitivity analyses were performed to evaluate the robustness of the results.

The first analysis assessed whether prenatal stress and depression were associated with PBMC DNAm at 12 months to determine if the effects persisted over time. Second, the researchers adjusted for prenatal depression and stress in the corresponding postnatal models to control for possible confounding due to prenatal exposure. The third analysis used a composite adversity score for each time point to investigate the combined effects of depression and stress. This adversity score was created to capture the cumulative effects of maternal mental health on DNAm and developmental outcomes. Finally, the primary analysis was additionally adjusted for atopy status.

Findings

Overall, the study included 131 infants with DNAm data at birth and 12 months; the cohort predominantly consisted of children from higher socioeconomic backgrounds. The median depression and stress scores were generally low at antenatal and postpartum time points. The median depression score decreased postpartum, while the median stress score increased.

There was a significant association between prenatal depression and differential CBMC DNAm at two CpG sites and between prenatal stress and differential CBMC DNAm at eight CpG sites; only one CpG site was common to both prenatal stress and depression. Furthermore, significant associations were observed between postnatal depression and differential PBMC DNAm at 11 CpG sites.

In addition, there were significant associations between postnatal stress and differential PBMC DNAm at eight CpG sites. There was no overlap in CpG sites between postnatal depression and stress. Sensitivity analyses revealed that most of these associations remained significant even after adjusting for prenatal exposure or atopy status, highlighting the robustness of the findings.

Finally, two CpG sites were associated with prenatal adversity, and seven CpG sites were associated with postnatal adversity, as determined by the composite adversity score. The persistence of these findings across analyses suggests that cumulative exposure to maternal stress and depression could have a stronger impact on DNAm than individual exposures alone.

Conclusions

The findings illustrate significant associations of maternal depression and stress with differential DNAm in the first year of life. The study identified eight and two CpG sites associated with prenatal stress and depression, respectively. Moreover, eight and 11 CpG sites were associated with postnatal stress and depression, respectively.

Overall, the results indicate that maternal depression and stress are associated with epigenomic changes in the child in the first year of life. These epigenetic modifications could lead to alterations in gene expression, potentially affecting downstream biological pathways that influence developmental and health outcomes. Further studies are necessary to corroborate these findings and elucidate the underlying mechanisms.

The authors also noted several limitations, including the relatively small sample size, the lack of replication in other studies, and the fact that DNAm changes were observed in blood cells, which may not fully capture tissue-specific effects such as those occurring in the brain. Despite these limitations, the study contributes valuable insights into the role of maternal mental health in shaping the epigenome of the child during critical early developmental periods.