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FRIMEDBIO-Fri prosj.st. med.,helse,biol

Re-thinking the programming hypothesis: Prenatal maternal anxiety/depression, DNA methylation and child psychopathology. A sibling design.

Alternative title: Prenatalt stress, DNA metylering og barns utvikling. Et søsken design.

Awarded: NOK 8.2 mill.

Project Number:

301004

Project Period:

2020 - 2025

Location:

Partner countries:

Depression and anxiety disorders are among the most common disorders to inflict the expecting mother during pregnancy, and mothers to be are continuously warned about the potential hazard that could inflict the unborn child. Although the consequences of exposure to maternal anxiety and depression on child development have been well documented, the causal mechanism explaining this link is not well understood. Accordingly, the aim of this study is to gain new knowledge about some of the mechanisms underlying the link between prenatal anxiety and depression and later outcomes in the child. In this study we will use a quasi-experimental approach with genotype and DNA methylation to address some of the current challenges in research examining exposure to prenatal stress or adversity on child psychopathology. We will include data from a longitudinal cohort study, The Norwegian Mother and Child Cohort (MoBa). This cohort consists of N=270 000 (mother, father, child). We will use available genotype data, and DNA methylation samples of 1200 siblings combined with high-quality prospective measures of psychopathology covering both symptoms and disorders, from pregnancy to age 8. This project provides a unique opportunity to unravel the independent effects of the in utero environment on development, whilst controlling for the postnatal environment and taking genetic factors into consideration. Thus the project findings will inform clinicians and practitioners to help mothers and their children off to a better start, and in the long-term help invest in risk reduction and sustainable health care for families using a more targeted and personalised approach.

Depression and anxiety disorders are among the most common disorders to inflict the expecting mother during pregnancy, with a prevalence of 7 to 18% (Bauer et al., 2014). During the past half-century animal research and parallel human findings suggest that prenatal exposure to maternal stress, anxiety and depression influence offspring psychopathology (Barker et al., 2018). Although, the consequences of exposure to maternal anxiety and depression on child development have been well documented, the causal mechanism explaining this link is not well understood. Accordingly, the aim of this proposal is to gain new knowledge in some of the mechanisms underlying the link between prenatal anxiety and depression and later outcomes in the child. The purpose of this project is to examine the role of epigenetic changes in the link between prenatal maternal anxiety/depression and child psychoapathology. Whilst several studies have examined the role of epigenetic changes in children exposed to prenatal anxiety and depression (Barker et al, 2018), findings have been limited by small sample size, and the lack of adequate control group matched for family environment. In this study we will examine the role of DNAm in the association between prenatal maternal anxiety/depression and child psychopathology from infancy to middle childhood, in a discordant sibling design (N=1200). The large sibling sample in the MoBa cohort has unique information for each pregnancy, and therefore, provides an opportuinity to select optimal sibling pairs. Thus, 600 exposed children will be compared with their non-exposed sibling. We expect that our findings will extend current knowledge on the role of prenatal programming and DNA methylation on pathways to healthy and aberrant development, and provide new knowledge about how epigenetic mechanisms may render some infants more susceptible to adversity and simultaneously more likely to benefit from supportive experience.

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Funding scheme:

FRIMEDBIO-Fri prosj.st. med.,helse,biol

Funding Sources