Identifying reproducible sex-based differences in the human brain

2020

Challenge

Scientists have long known that the brains of male and female mice show consistent anatomical differences on brain scans and in lab experiments. However, brain differences based on biological sex in humans have not been as consistently identified.

Advance

IRP researchers led by Siyuan Liu, Ph.D., and Armin Raznahan, M.D., Ph.D., led the first study to show consistent sex differences in the human brain across different sets of participants and to link those differences to patterns of gene activity in the brain. The study analyzed publicly accessible data from 2,000 brain scans of healthy adults. Some of the brains areas that differed in men and women were involved in tasks like facial recognition that show gender differences in performance. Moreover, the anatomical differences identified in the study were remarkably consistent across different groups of participants, and the way these changes were arranged corresponded to the activity of the sex-determining X and Y chromosomes.

Impact

Sex differences in brain anatomy appear to be an enduring legacy of mammalian evolution, as shown by their consistency across species, from mice to humans. By shedding new light on the genetic mechanisms underlying sex-based differences in brain anatomy, these findings open new doors for future investigations of how the influence of sex-related genes contributes to sex-based differences in neurological and psychiatric illnesses and human behavior more generally.

Publications

Liu S, Seidlitz J, Blumenthal JD, Clasen LS, Raznahan A. (2020). Integrative structural, functional and transcriptomic analyses of sex-biased brain organization in humans. PNAS. Aug 4;117(31)18788-18798. doi: 10.1073/pnas.1919091117