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Sex differences in Variability of Brain Structure Across the Lifespan

By Natalie J. Forde, Jerrold Jeyachandra, Michael Joseph, Grace R Jacobs, Erin Dickie, Theodore D Satterthwaite, Russell T Shinohara, Stephanie H Ameis, Aristotle Voineskos

Posted 15 Nov 2019
bioRxiv DOI: 10.1101/842567 (published DOI: 10.1093/cercor/bhaa123)

Several brain disorders exhibit sex differences in onset, presentation, and prevalence. Increased understanding of the neurobiology of sex-based differences in variability across the lifespan can provide insight into both disease vulnerability and resilience. In n=3,069 participants, from 8-95 years of age, we first analyzed the variance ratio in females versus males of cortical surface area and global and subcortical volumes for discrete brain regions, and found widespread greater variability in males. In contrast, variance in cortical thickness was similar for males and females. These findings were supported by multivariate analysis accounting for structural covariance, and present and stable across the lifespan. We then examined variability among brain regions by sex. We found significant age-by-sex interactions across neuroimaging metrics, whereby in very early life males had reduced among-region variability compared to females, while in very late life this was reversed. Overall, our findings of greater regional variability but less among-region variability in males in early life may aid our understanding of sex-based risk for neurodevelopmental disorders. In contrast, our findings in late life may provide a potential sex-based risk mechanism for dementia.

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