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Neuroimage. 2019 Aug 27:116122. doi: 10.1016/j.neuroimage.2019.116122. [Epub ahead of print]

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

Author information

1
Developmental Neurogenomics Unit, Human Genetics Branch, National Institute of Mental Health, Bethesda, MD, 20892, USA.
2
Department of Medical Biophysics, University of Toronto, Toronto, ON, M5T 1R8, Canada; Neurosciences and Mental Health, the Hospital for Sick Children, Toronto, ON, M5T 3H7, Canada.
3
Cerebral Imaging Centre, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada, H3A OG4; Departments of Psychiatry and Biological and Biomedical Engineering, McGill University, Montreal, QC, H3A OG4, Canada.
4
Department of Biostatistics, Epidemiology, and Informatics, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
5
Developmental Neurogenomics Unit, Human Genetics Branch, National Institute of Mental Health, Bethesda, MD, 20892, USA. Electronic address: raznahana@mail.nih.gov.

Abstract

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 bring greater resolution to our spatiotemporal understanding of amygdalo-hippocampal development in healthy males and females and discover focal sex-differences in the structural maturation of the brain components that may contribute to differences in behavior and psychopathology that emerge during adolescence.

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