Prenatal maternal depressive symptoms and infant DNA methylation: a longitudinal epigenome-wide study.

Background: Prenatal maternal stress increases the risk of offspring developmental and psychological difficulties. The biological mechanisms behind these associations are mostly unknown. One explanation suggests that exposure of the fetus to maternal stress may influence DNA methylation. However, this hypothesis is largely based on animal studies, and human studies of candidate genes from single timepoints. Aim: The aim of this study was to investigate if prenatal maternal stress, in the form of maternal depressive symptoms, was associated with variation in genome-wide DNA methylation at two timepoints. Methods: One-hundred and eighty-four mother-child dyads were selected from a population of pregnant women in the Little-in-Norway study. The Edinburgh Postnatal Depression Scale (EPDS) measured maternal depressive symptoms. It was completed by the pregnant mothers between weeks 17 and 32 of gestation. DNA was obtained from infant saliva cells at two timepoints (age 6 weeks and 12 months). DNA methylation was measured in 274 samples from 6 weeks (n = 146) and 12 months (n = 128) using the Illumina Infinium HumanMethylation 450 BeadChip. Linear regression analyses of prenatal maternal depressive symptoms and infant methylation were performed at 6 weeks and 12 months separately, and for both timepoints together using a mixed model. Results: The analyses revealed no significant genome-wide association between maternal depressive symptoms and infant DNA methylation in the separate analyses and for both timepoints together. Conclusions: This sample of pregnant women and their infants living in Norway did not reveal associations between maternal depressive symptoms and infant DNA methylation.

Can Early Life Stress Engender Biological Resilience?: Commentary.

Early life is a sensitive period in which social experience provides essential information for normal development (Johnson and Blasco Pediatrics in Review, 18(7), 224-242, 1997). Studies have shown that having a loving, primary caregiver early in life acts as a protective factor against social and emotional maladjustments later in life (Egeland and Hiester Child Development, 66(2), 474-485, 1995), while the exposure to childhood adversities, such as child abuse and neglect, have been associated with increased risk of developing diseases later in life (Felitti et al. American Journal of Preventive Medicine, 14(4), 245-258, 1998). Data based on reports by American child protective service agencies estimated that with little change over the last four years, more than 700,000 children were victims of child abuse and neglect in the US alone every year (Child Trends Data Bank 2019). The biological mechanisms involved in the associations between childhood adversities and disease development are not known, but it is likely that child abuse and neglect do influence fundamental biological processes (Mehta et al. Proceedings of the National Academy of Sciences of the United States of America, 110(20), 8302-8307, 2013) and epigenetic alteration has been suggested as one such biological mechanism regulating these interactions (Tammen et al. Molecular Aspects of Medicine, 34(4), 753-764, 2013).

DNA methylation changes in infants between 6 and 52 weeks.

Infants undergo extensive developments during their first year of life. Although the biological mechanisms involved are not yet fully understood, changes in the DNA methylation in mammals are believed to play a key role. This study was designed to investigate changes in infant DNA methylation that occurs between 6 and 52 weeks. A total of 214 infant saliva samples from 6 or 52 weeks were assessed using principal component analyses and t-distributed stochastic neighbor-embedding algorithms. Between the two time points, there were clear differences in DNA methylation. To further investigate these findings, paired two-sided student's t-tests were performed. Differently methylated regions were defined as at least two consecutive probes that showed significant differences, with a q-value < 0.01 and a mean difference > 0.2. After correcting for false discovery rates, changes in the DNA methylation levels were found in 42 genes. Of these, 36 genes showed increased and six decreased DNA methylation. The overall DNA methylation changes indicated decreased gene expression. This was surprising because infants undergo such profound developments during their first year of life. The results were evaluated by taking into consideration the extensive development that occurs during pregnancy. During the first year of life, infants have an overall three-fold increase in weight, while the fetus develops from a single cell into a viable infant in 9 months, with an 875-million-fold increase in weight. It is possible that the findings represent a biological slowing mechanism in response to extensive fetal development. In conclusion, our study provides evidence of DNA methylation changes during the first year of life, representing a possible biological slowing mechanism. We encourage future studies of DNA methylation changes in infants to replicate the findings by using a repeated measures model and less stringent criteria to see if the same genes can be found, as well as investigating whether other genes are involved in development during this period.

Are unpopular children more likely to get sick? Longitudinal links between popularity and infectious diseases in early childhood.

Social stress and inflammatory processes are strong regulators of one another. Considerable evidence shows that social threats trigger inflammatory responses that increase infection susceptibility in both humans and animals, while infectious disease triggers inflammation that in turn regulates social behaviours. However, no previous study has examined whether young children's popularity and their rate of infectious disease are associated. We investigated the longitudinal bidirectional links between children's popularity status as perceived by peers, and parent reports of a variety of infectious diseases that are common in early childhood (i.e. common cold as well as eye, ear, throat, lung and gastric infections). We used data from the 'Matter of the First Friendship Study' (MOFF), a longitudinal prospective multi-informant study, following 579 Norwegian pre-schoolers (292 girls, median age at baseline = six years) with annual assessments over a period of three years. Social network analysis was used to estimate each child's level of popularity. Cross-lagged autoregressive analyses revealed negative dose-response relations between children's popularity scores and subsequent infection (b = -0.18, CI = -0.29, -0.06, and b = -0.13, CI = -0.23, -0.03). In conclusion, the results suggest that children who are unpopular in early childhood are at increased risk of contracting infection the following year.

The Association between Hair Cortisol and Self-Reported Symptoms of Depression in Pregnant Women.

Depression has been linked to an imbalance in cortisol. Until recently, cortisol has been studied by measuring concentrations at single time points in blood or saliva samples. Cortisol concentrations vary with circadian rhythm and experiences, from time point to time point. The measurement of hair cortisol concentration (HCC) is a new method of accessing mean, long-term cortisol concentrations. Recent studies show positive associations between depression and HCC, and prenatal maternal cortisol is thought to influence the developing fetus. We therefore examined the association between HCC and self-reported symptoms of depression in second trimester pregnant women. Participants were 181 women, recruited between September 2011 and October 2013 to the Little-in-Norway (LiN)-study. These women answered the Edinburgh Postnatal Depression Rating Scale (EPDS) on self-reported symptoms of depression, and one cm maternal scalp hair was collected and analyzed for cortisol concentrations. Multiple regression analyses did not show depressive symptoms as a predictor for HCC in our selection of pregnant women, while gestational age was significantly related. In conclusion, our study indicated that symptoms of depression during pregnancy did not predict HCC, but further studies of clinically depressed, pregnant women using gestational age as an adjustment variable are warranted.