Neonatal amygdalae and hippocampi are influenced by genotype and prenatal environment, and reflected in the neonatal DNA methylome

Genes Brain Behav. 2019 Sep;18(7):e12576. doi: 10.1111/gbb.12576. Epub 2019 May 15.


The amygdala and hippocampus undergo rapid development in early life. The relative contribution of genetic and environmental factors to the establishment of their developmental trajectories has yet to be examined. We performed imaging on neonates and examined how the observed variation in volume and microstructure of the amygdala and hippocampus varied by genotype, and compared with prenatal maternal mental health and socioeconomic status. Gene × Environment models outcompeted models containing genotype or environment only to best explain the majority of measures but some, especially of the amygdaloid microstructure, were best explained by genotype only. Models including DNA methylation measured in the neonate umbilical cords outcompeted the Gene and Gene × Environment models for the majority of amygdaloid measures and minority of hippocampal measures. This study identified brain region-specific gene networks associated with individual differences in fetal brain development. In particular, genetic and epigenetic variation within CUX1 was highlighted.

Keywords: developmental trajectory; diffusion tensor imaging; epigenetics; magnetic resonance imaging; neonatal brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / diagnostic imaging
  • Amygdala / metabolism*
  • DNA Methylation*
  • Epigenesis, Genetic
  • Female
  • Gene-Environment Interaction*
  • Genotype
  • Hippocampus / diagnostic imaging
  • Hippocampus / metabolism*
  • Homeodomain Proteins / genetics
  • Humans
  • Infant, Newborn
  • Male
  • Pregnancy
  • Prenatal Exposure Delayed Effects / genetics*
  • Repressor Proteins / genetics
  • Stress, Psychological / genetics*
  • Transcription Factors / genetics


  • CUX1 protein, human
  • Homeodomain Proteins
  • Repressor Proteins
  • Transcription Factors