Childhood maternal care is associated with DNA methylation of the genes for brain-derived neurotrophic factor (BDNF) and oxytocin receptor (OXTR) in peripheral blood cells in adult men and women

Abstract

In adults, reporting low and high maternal care in childhood, we compared DNA methylation in two stress-associated genes (two target sequences in the oxytocin receptor gene, OXTR; one in the brain-derived neurotrophic factor gene, BDNF) in peripheral whole blood, in a cross-sectional study (University of Basel, Switzerland) during 2007-2008. We recruited 89 participants scoring < 27 (n = 47, 36 women) or > 33 (n = 42, 35 women) on the maternal care subscale of the Parental Bonding Instrument (PBI) at a previous assessment of a larger group (N = 709, range PBI maternal care = 0-36, age range = 19-66 years; median 24 years). 85 participants gave blood for DNA methylation analyses (Sequenom(R) EpiTYPER, San Diego, CA) and cell count (Sysmex PocH-100i™, Kobe, Japan). Mixed model statistical analysis showed greater DNA methylation in the low versus high maternal care group, in the BDNF target sequence [Likelihood-Ratio (1) = 4.47; p = 0.035] and in one OXTR target sequence Likelihood-Ratio (1) = 4.33; p = 0.037], but not the second OXTR target sequence [Likelihood-Ratio (1) < 0.001; p = 0.995). Mediation analyses indicated that differential blood cell count did not explain associations between low maternal care and BDNF (estimate = -0.005, 95% CI = -0.025 to 0.015; p = 0.626) or OXTR DNA methylation (estimate = -0.015, 95% CI = -0.038 to 0.008; p = 0.192). Hence, low maternal care in childhood was associated with greater DNA methylation in an OXTR and a BDNF target sequence in blood cells in adulthood. Although the study has limitations (cross-sectional, a wide age range, only three target sequences in two genes studied, small effects, uncertain relevance of changes in blood cells to gene methylation in brain), the findings may indicate components of the epiphenotype from early life stress.

Maternal adversities during pregnancy and cord blood oxytocin receptor (OXTR) DNA methylation

“…Furthermore, we found that exposure to acute psychosocial stress was associated with a short-term increase in OXTR methylation, followed by a decrease during the stress recovery period (Unternaehrer et al, 2012). Finally, adults reporting low maternal care during childhood had elevated levels of DNA methylation in one of two examined OXTR target sequences (Unternaehrer et al, 2015).…”

Oxytocin pathways in the intergenerational transmission of maternal early life stress

“…Moreover, there was a significant main effect of rs53576 genotype on OXTR exon 2 methylation – women carrying the A allele had significantly higher methylation status than GG homozygous individuals. Importantly, there is evidence that early maternal care is associated with differential methylation of regions in the OXTR gene of adults (Unternaehrer et al, 2015). In one target sequence positioned at exon 3 of the OXTR gene, there was a negative association between maternal care and blood-derived OXTR DNA-methylation levels.…”

“…DNA methylation of the OXTR gene may be moderated by environmental contingencies, like poor maternal care in childhood (Beery et al, 2015; Unternaehrer et al, 2015), and genotype (Bell et al, 2015). However, comparability between studies is difficult because they differ greatly in target sequences and partly show effects that are not in the expected direction.…”

Cord Blood DNA Methylation Biomarkers for Predicting Neurodevelopmental Outcomes

“…In humans, poor maternal care provision has also been associated with altered DNA methylation. Increased methylation of the BDNF and oxytocin receptor genes in whole blood has been observed in adults who report low maternal care provision during the first 16 years of life [78]. Notably, changes in DNA methylation were only observed in some regions of these genes but not others, indicating a specific DNA methylation response to this exposure.…”