A Study Finds Sex Differences in the Brain. Does It Matter?

For Armin Raznahan, publishing research on sex differences is a fraught proposition. Now chief of the section on developmental neurogenomics at the National Institutes of Health, Raznahan learned early that searching for dissimilarities between men’s and women’s brains can have unintended effects. “I got my fingers burned when I first started,” Raznahan says. As a PhD student, he published a study that examined structural differences between men’s and women’s brains and how they changed with age. “We observed a particular pattern, and we were very cautious about just describing it, as one should be, not jumping to functional interpretations,” he says. Despite his efforts, The Wall Street Journal soon published an article that cited his study in a defense of single-sex schooling, under the assumption that boys and girls must learn in distinct ways because their brain anatomy is slightly different. “That really threw me,” he says. “The experience has stayed with me.”
Nevertheless, Raznahan has continued to study sex differences, in the hope that they could help us better understand neurodevelopmental disorders. He focuses on people with sex chromosome aneuploidy, or any variation other than XX (typically female) and XY (typically male). People with genetic variations (such as XXY) have an inflated risk of autism spectrum disorder, ADHD, and anxiety, among other ailments. Raznahan’s hope is that uncovering if and how men’s and women’s brains differ—for example, in the sizes of regions or the strengths of the connections among them—could help us figure out why people with aneuploidy are more likely to experience neurodevelopmental and psychiatric concerns. Solving this puzzle could be a step toward unlocking the perplexing mystery of psychiatric illness.
Last Monday, he and his team published a study in Proceedings of the National Academy of Sciences that not only reported reliable sex differences in the volumes of certain parts of men’s and women’s brains but also tied those differences to the direct influence of sex chromosomes. “What we were seeking to do in this study is ask some relatively simple questions that hadn’t quite ever been directly addressed,” Raznahan says. “How reproducible are anatomical sex differences in the human brain? And what sorts of functional systems, if any, do they seem to be co-localized with?”To attack these questions, Raznahan and his team didn’t collect their own data; rather, they leveraged the Human Connectome Project, which collects brain scans taken from over 1,000 participants at several institutions. Using conventional MRI data, they compared how much gray matter—the tissue containing the cell bodies of most neurons—the sampled men and women had in various brain regions. While most regions looked similar, in some spots, either men or women seemed to have more gray matter.
By comparing their results to another large data set, Raznahan’s team found that these brain regions were associated with areas where genes on the sex chromosomes are disproportionately expressed. For Raznahan, this potential link between chromosomes and brain structure is particularly exciting. “If we can understand the biology of sex better, maybe those pathways are going to help us understand what is happening to put a person at risk of manifesting symptoms of autism spectrum disorder, for example,” he says.
But other scholars question the idea that this sort of research will help us understand mental disorders. Lise Eliot, a professor of neuroscience at Rosalind Franklin University, believes that sex differences in the prevalence of some disorders might be better explained by biases among doctors, or in the diagnostic criteria, rather than by biology. Proponents of sex difference research often note that boys are diagnosed with autism about four times as often as girls, but Eliot questions the relevance of that statistic. “I think a lot of that is just diagnostic bias,” she says. “The definition of the disorder is based on a male stereotype.”