Epigenetic dynamics in infancy and the impact of maternal engagement

Kathleen M Krol, Robert G Moulder, Travis S Lillard, Tobias Grossmann, Jessica J Connelly, Kathleen M Krol, Robert G Moulder, Travis S Lillard, Tobias Grossmann, Jessica J Connelly

Abstract

The contribution of nature versus nurture to the development of human behavior has been debated for centuries. Here, we offer a piece to this complex puzzle by identifying the human endogenous oxytocin system-known for its critical role in mammalian sociality-as a system sensitive to its early environment and subject to epigenetic change. Recent animal work suggests that early parental care is associated with changes in DNA methylation of conserved regulatory sites within the oxytocin receptor gene (OXTRm). Through dyadic modeling of behavior and OXTRm status across the first year and a half of life, we translated these findings to 101 human mother-infant dyads. We show that OXTRm is dynamic in infancy and its change is predicted by maternal engagement and reflective of behavioral temperament. We provide evidence for an early window of environmental epigenetic regulation of the oxytocin system, facilitating the emergence of individual differences in human behavior.

Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

Figures

Fig. 1. Infant OXTR m changes across…
Fig. 1. Infant OXTRm changes across infancy.
Plotted are the frequency distributions of OXTRm change scores for mothers (magenta) and infants (orange). Change scores were calculated by subtracting methylation levels at the 5-month visit from methylation levels at the 18-month visit. Scores above zero indicate an increase in OXTRm over time, while scores below zero represent a decrease. Infants display nearly double the amount of change (range = 17.60; P = 0.04) than that displayed in mothers (range = 9.70; P = 0.61).
Fig. 2. Maternal engagement predicts a reduction…
Fig. 2. Maternal engagement predicts a reduction in infant OXTRm over time.
(A) Full model. An actor-partner interdependence model was used to test the effect of maternal and infant behavioral engagement on maternal and infant OXTRm change. To separate meaningful variation from measurement error, we created latent variables for the methylation data derived from values from three technical replicates (labeled Rep. 1 to Rep. 3 in the figure) (RMSEA = 0.0, CFI = 1, and TLI = 1). Single-headed linear arrows are labeled with standardized β coefficients, indicating directionality. Covariances are represented by double-headed linear arrows and indicate no directionality. Double-headed, curved error paths pointing to each respective variable represent the residual variance within each variable not accounted for by the model paths. (B) Reduced model. Path removal was used to determine the driving paths of the model (RMSEA = 0.0, CFI = 1, and TLI = 1). This model does not significantly differ from the full model (P = 0.516). Even when taking into account the positive covariance between infant and maternal engagement at 5 months, only maternal engagement predicts infant OXTRm change (reduction) from 5 to 18 months (β = −0.30).
Fig. 3. Maternal engagement fine-tunes infant OXTR…
Fig. 3. Maternal engagement fine-tunes infant OXTRm from 5 to 18 months, which in turn associates with overt infant temperament at 18 months.
(A) Plotted is the association between maternal engagement at 5 months (x axis) and infant OXTRm change from 5 to 18 months (y axis). The slope of the regression line is the predicted β value derived from the actor-partner interdependence model (β = −0.30, P = 0.009). Note that engagement and methylation scores were standardized for this analysis (Z score transformed). (B) Scatterplot visualizing the association between infant OXTRm at 18 months and temperamental discomfort (log transformed) as measured by the Early Childhood Behavior Questionnaire (ECBQ) (17), r(80) = 0.293, P = 0.008. The discomfort subscale of the ECBQ measures the amount of negative affect one’s infant feels toward certain sensory qualities of stimulation, such as complexity, rate, and intensity of sounds, light, and textures. Shaded orange bar represents the 95% confidence interval.

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