Raznahan and his colleagues do have a biological theory about what’s behind the gray matter differences they observed. They used data on the brain’s transcriptome, or the genes that are preferentially turned on to make proteins in each brain region, to determine which genes appeared to be more active in the areas where they observed the biggest differences. One pair of chromosomes stood out from all the rest: the sex chromosomes. Unlike the others, they were markedly more active in areas where men had more gray matter than women, as compared with the rest of the brain.
“It certainly doesn’t prove that the sex [chromosomes] are causally relevant for the anatomical sex differences, but it’s more guilt by spatial association,” Raznahan says. Like a detective who always observes the same person at the scene of the crime, Raznahan has reason to be suspicious that the chromosomes’ expression has an influence on differences in gray matter volume when they show up in the same brain region—but no direct proof.
If Raznahan’s hypothesis about the chromosomes’ role is correct, it could have a substantial influence on sex difference research. According to de Vries, scientists have long assumed that sex chromosomes don’t have a direct effect on brain structure. Rather, he says, their presumed influence was more circuitous: Genes would give rise to the gonads, which would then secrete hormones that could influence brain development. The going idea, he says, has been “that what genes do is they determine that there’s going to be a testis or an ovary. And once you’ve made that decision, the hormones take over.”
But Raznahan’s observations seem to suggest that sex chromosomes could influence brain anatomy without hormones acting as a mediator. “The fact he’s finding genes that are on sex chromosomes,” McCarthy says, “is really very exciting and very novel, because we so much emphasize the role of gonadal steroids.” (These are hormones like estrogen and testosterone.)
Nevertheless, the study falls short of demonstrating that these chromosomes have an effect on structure. Correlation is simply not the same as causation. Raznahan’s work, says de Vries, “doesn’t necessarily suggest that these sex chromosomal genes cause these differences.”
What else could have played the critical role? Possibly environmental factors, like gender roles or the psychological stressors of belonging to an oppressed group. Just as the London cab drivers experienced remarkable changes in brain anatomy as they learned the complex layout of their city, so too might men’s and women’s brains change in response to the particular demands placed on them by their societies. “No one’s exploring the actual environment side, because it’s a lot harder to do,” Eliot says. But Raznahan, de Vries, and McCarthy agree that an environmental explanation is unlikely.
No matter what the cause might be, all of the researchers agree that it would be hard to generalize from this study to the entire world population. The data sets the researchers used came from the US and the UK, which are both wealthy, predominantly white countries. “The whole of neuroscience and genetics is so heavily skewed in terms of its cultural representation,” Raznahan says. “How these features might vary or remain the same across different societal structures would be a really important thing to look at. It’s challenging because the data just aren’t there.”