Grandmotherhood is associated with reduced OXTR DNA methylation

Abstract

In mammals, both parental and alloparental care are associated with increased brain oxytocin signaling. Grandmothers are important alloparents in many human families. Based on animal model research showing that peripheral Oxtr methylation is associated with Oxtr expression in the nucleus accumbens, we investigated whether grandmaternal caregiving is associated with lower peripheral OXTR methylation. Results reveal several regions within OXTR where grandmothers have lower DNA methylation compared with non-grandmother controls, and no regions where grandmothers have higher OXTR DNA methylation. Among grandmothers, OXTR methylation was most strongly correlated with the grandmother's assessment of the degree of positive feelings between her and the grandchild, which in turn predicted caregiving engagement. Although there was little evidence that grandmaternal OXTR methylation modulated grandmaternal neural responses to viewing photos of the grandchild within brain regions involved in caregiving motivation, it was negatively correlated with the neural response to an unknown grandchild. Thus, while OT signaling may not be essential for activating grandmaternal brain reward systems in our low-stress experimental context, it may support caregiving motivation towards unrelated children. Future longitudinal research should determine whether the transition to grandmotherhood is associated with a reduction in OXTR methylation.

Keywords: Grandmother; Methylation; Oxytocin.

Figure 1:

Raincloud plot of OXTR methylation in fathers and nonfathers. The large red and blue dots represent the mean value for controls and grandmothers, respectively. The attached horizontal bars represent +/− 1 standard error.

Figure 2:

Schematic of OXTR gene, illustrating the location of two differential methylated regions along with MT2, −901, −924 and −934. DMR1 and DMR2 are shaded red. MT2 is shaded blue. −901, −924 and −934 are shaded pink.

Figure 3:

(a) Scatterplot of the relationship between grandmaternal positive affect and % DNA methylation within DMR2. Symbol size and color density is proportional to the number of overlapping data points. (b) The mediation effect of the positive affect towards grandchildren linking OXTR methylation levels in DMR2 region and grandmaternal caregiving engagement. All paths (a, b, and c’) and mediation effects (path a*b) are labeled with unstandardized path coefficients and their corresponding standard errors in parenthesis. ***p <.001.

Figure 4:

DMR2 DNA methylation and grandmaternal brain function. A) Voxels within the SN/VTA ROI where (log) DMR2 methylation is positively correlated with the contrast (Own – Unknown Grandchild), voxels in red survive correction for the number of voxels over which statistical tests were conducted (corrected p<0.05), while voxels in yellow additionally survive correction for the five methylation variables that were analyzed (corrected p<0.01) B) scatterplot of relationship between log DMR2 methylation and the SN/VTA response for the contrast (Own – Unknown Grandchild) (yellow voxels in A), C) scatterplot of the relationship between log DMR2 methylation and the SN/VTA response to the own grandchild (filled circles) and the unknown grandchild (open circles) relative to the unmodeled baseline. The SN/VTA response is averaged across all activated voxels from within the SN/VTA mask.