Sex-biased trajectories of amygdalo-hippocampal morphology change over human development

Neuroimage. 2020 Jan 1;204:116122. doi: 10.1016/j.neuroimage.2019.116122. Epub 2019 Aug 27.


The amygdala and hippocampus are two adjacent allocortical structures implicated in sex-biased and developmentally-emergent psychopathology. However, the spatiotemporal dynamics of amygdalo-hippocampal development remain poorly understood in healthy humans. The current study defined trajectories of volume and shape change for the amygdala and hippocampus by applying a multi-atlas segmentation pipeline (MAGeT-Brain) and semi-parametric mixed-effects spline modeling to 1,529 longitudinally-acquired structural MRI brain scans from a large, single-center cohort of 792 youth (403 males, 389 females) between the ages of 5 and 25 years old. We found that amygdala and hippocampus volumes both follow curvilinear and sexually dimorphic growth trajectories. These sex-biases were particularly striking in the amygdala: males showed a significantly later and slower adolescent deceleration in volume expansion (at age 20 years) than females (age 13 years). Shape analysis localized significant hot-spots of sex-biased anatomical development in sub-regional territories overlying rostral and caudal extremes of the CA1/2 in the hippocampus, and the centromedial nuclear group of the amygdala. In both sexes, principal components analysis revealed close integration of amygdala and hippocampus shape change along two main topographically-organized axes - low vs. high areal expansion, and early vs. late growth deceleration. These results (i) bring greater resolution to our spatiotemporal understanding of amygdalo-hippocampal development in healthy males and females, and (ii) uncover focal sex-differences in the structural maturation of the brain components that may contribute to differences in behavior and psychopathology that emerge during adolescence.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Amygdala* / anatomy & histology
  • Amygdala* / diagnostic imaging
  • Amygdala* / growth & development
  • Atlases as Topic
  • Child
  • Child, Preschool
  • Female
  • Hippocampus* / anatomy & histology
  • Hippocampus* / diagnostic imaging
  • Hippocampus* / growth & development
  • Human Development / physiology*
  • Humans
  • Longitudinal Studies
  • Male
  • Neuroimaging / methods*
  • Sex Characteristics*
  • Young Adult