Maternal prenatal depressive symptoms predict infant NR3C1 1F and BDNF IV DNA methylation

Abstract

Prenatal maternal psychological distress increases risk for adverse infant outcomes. However, the biological mechanisms underlying this association remain unclear. Prenatal stress can impact fetal epigenetic regulation that could underlie changes in infant stress responses. It has been suggested that maternal glucocorticoids may mediate this epigenetic effect. We examined this hypothesis by determining the impact of maternal cortisol and depressive symptoms during pregnancy on infant NR3C1 and BDNF DNA methylation. Fifty-seven pregnant women were recruited during the second or third trimester. Participants self-reported depressive symptoms and salivary cortisol samples were collected diurnally and in response to a stressor. Buccal swabs for DNA extraction and DNA methylation analysis were collected from each infant at 2 months of age, and mothers were assessed for postnatal depressive symptoms. Prenatal depressive symptoms significantly predicted increased NR3C1 1F DNA methylation in male infants (β = 2.147, P = 0.044). Prenatal depressive symptoms also significantly predicted decreased BDNF IV DNA methylation in both male and female infants (β = -3.244, P = 0.013). No measure of maternal cortisol during pregnancy predicted infant NR3C1 1F or BDNF promoter IV DNA methylation. Our findings highlight the susceptibility of males to changes in NR3C1 DNA methylation and present novel evidence for altered BDNF IV DNA methylation in response to maternal depression during pregnancy. The lack of association between maternal cortisol and infant DNA methylation suggests that effects of maternal depression may not be mediated directly by glucocorticoids. Future studies should consider other potential mediating mechanisms in the link between maternal mood and infant outcomes.

Keywords: BDNF; BDNF, gene encoding the brain-derived neurotrophic factor protein; BPA, bisphenol A; DNA methylation; GR, glucocorticoid receptor; HPA, hypothalamic-pituitary adrenal; NR3C1; NR3C1, gene encoding the glucocorticoid receptor; depression; early life adversity; fetal programming.

Figure 1.

Percent methylation at each CpG site (1–10) within the examined NR3C1 1F region for the depression-exposed and control infants. (A) shows the values for the male infants and (B) the female infants.

Figure 2.

Percent methylation at each CpG site within the examined BDNF IV region for the depression-exposed and control infants.

Figure 3.

Schematic and the analyzed sequence of the NR3C1 (A) and BDNF (B) gene. Shown are specific CpG sites analyzed using bisulfite-pyrosequencing assays as well as NGFI-A (blue box) and CREB (purple box) binding sites within NR3C1 exon 1F and BDNF promoter IV, respectively.