Study Shows Highly Reproducible Sex Differences in Aspects of Human Brain Anatomy

A scientific analysis of more than 2,000 brain scans found evidence for highly reproducible sex differences in the volume of certain regions in the human brain. This pattern of sex-based differences in brain volume corresponds with patterns of sex-chromosome gene expression observed in postmortem samples from the brain’s cortex, suggesting that sex chromosomes may play a role in the development or maintenance of sex differences in brain anatomy. The study, led by researchers at the National Institute of Mental Health (NIMH), part of the National Institutes of Health, is published in Proceedings of the National Academy of Sciences.

“Developing a clearer understanding of sex differences in human brain organization has great importance for how we think about well-established sex differences in cognition, behavior, and risk for psychiatric illness. We were inspired by new findings on sex differences in animal models and wanted to try to close the gap between these animal data and our models of sex differences in the human brain,” said Armin Raznahan, M.D., Ph.D., study co-author and chief of the NIMH Section on Developmental Neurogenomics.

Researchers have long observed consistent sex-based differences in subcortical brain structures in mice. Some studies have suggested these anatomical differences are largely due to the effects of sex hormones, lending weight to a “gonad-centric” explanation for sex-based differences in brain development. However, more recent mouse studies have revealed consistent sex differences in cortical structures, as well, and gene-expression data suggest that sex chromosomes may play a role in shaping these anatomical sex differences. {snip}

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“Males and females differ on many genetic and environmental factors that could all potentially influence brain development. Because it is challenging to experiment in humans, we often rely on observational data to infer potential genetic or environmental drivers of brain sex differences,” said Raznahan. “The fact that we observed a very high level of reproducibility of anatomical sex differences across different groups of males and females, and a link between these differences and sex chromosome gene expression, suggests these differences are likely not primarily the result of environmental effects alone.”

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Taken together, these findings shed light on the mechanisms that may contribute to sex-based differences in brain anatomy and point to genetic factors that may contribute to sex-based differences in brain disease and behavior. With these correlational findings as a roadmap, future research can more efficiently investigate the causes and consequences of sex differences in the human brain.