Placental Gene Expression and Offspring Temperament Trajectories: Predicting Negative Affect in Early Childhood

Abstract

Exposure to prenatal stress increases offspring risk for long-term neurobehavioral impairments and psychopathology, such as Attention Deficit Hyperactivity Disorder (ADHD). Epigenetic regulation of glucocorticoid pathway genes may be a potential underlying mechanism by which maternal conditions 'program' the fetal brain for downstream vulnerabilities. The present study aims to investigate whether mRNA expression of glucocorticoid pathway genes in the placenta predict offspring negative affect during early childhood (between 6 and 24months). Participants include 318 mother-child dyads participating in a longitudinal birth cohort study. Placental mRNA expression of glucocorticoid pathway genes (HSD11B1, HSD11B2, NR3C1, NCOR2) were profiled and negative affect traits of the offspring were measured at 6, 12, 18, and 24months. HSD11B1 mRNA expression significantly predicted negative affect (β = -.09, SE = .04; p = .036), and Distress to Limitations trajectories (β = -.13, SE = .06; p = .016). NCOR2 mRNA expression significantly predicted Distress to Limitations (β = .43, SE = .21; p = .047), and marginally predicted Sadness trajectories (β = .39, SE = .21; p = .068). HSD11B2 and NR3C1 did not predict trajectories of Negative Affect or subscale scores. Infant negative affect traits were assessed via maternal self-report, and deviated from linearity across follow-up. mRNA expression of glucocorticoid pathway genes in the placenta may be a potentially novel tool for early identification of infants at greater risk for elevated negative affect. Further study is needed to validate the utility of mRNA expression of glucocorticoid pathway genes in the placenta.