Differences in gene expression in the brains of men and women may influence the risks of some diseases

This study seeks to understand why men and women have different susceptibilities to neuropsychiatric and neurodegenerative disorders. To do so, researchers analyzed 169 samples from 30 individuals (15 of each sex) in six specific regions of the cerebral cortex, which are known to exhibit volume differences between sexes. The study found no sex-related differences in the number of cells. Men and women have similar proportions of neurons and glia in these regions. However, they did find changes in gene expression. That is, although men and women have the same number of neurons in the various cortical areas studied, the genes within those neurons are 'switched on' or 'switched off' differently depending on sex. Essentially, the study suggests that brain differences are not a matter of the quantity of components, but rather how those components are structured and/or function at the molecular level.

The study identifies the critical points where sex influences gene expression. Specifically, more than 3,000 genes with sex-biased expression were identified, of which 133 showed highly consistent results; that is, they are expressed differently in men and women, regardless of the brain region or cell type analyzed. In particular, the fusiform cortex showed very marked differences between sexes. At the cellular level, they found more marked differences in glial cells than in excitatory neurons, and more so than in inhibitory neurons.

In this sense, the fusiform cortex is one of the areas with the greatest sexual dimorphism (differences in volume and functional characteristics), and given that this area is crucial for social cognition (recognizing faces and expressions), the differences in gene expression could explain why men and women process social or visual stimuli differently, or why they exhibit different vulnerabilities to disorders such as autism, where facial processing is often impaired.

One striking finding is that, although the genes on the sex chromosomes (X in women and Y in men) show the most obvious differences, autosomal genes (those on the other chromosomes) are subject to hormonal regulation. This means that the genetic signatures found are linked to hormone-sensitive mechanisms, as expected, and that these genetic differences are directly related to how the cerebral cortex is built and organized. In fact, 119 of the 133 critical genes are autosomal.

In short, the study demonstrates that biological sex leaves a clear transcriptomic imprint in the adult brain. It's not just about having different chromosomes, but about how various factors and hormones modify the activity of thousands of genes, directly influencing vulnerability to mental and neurological diseases (for example, women are more frequently affected by mood and anxiety disorders, migraines, Alzheimer's disease, and other dementias) and very likely laying the groundwork for the behavioral differences between men and women.

What this study makes clear is that sex is a key biological variable that must be considered in both preclinical research and medical practice. It's worth noting that, in this study, the sex of the donors was defined by karyotype. That is, the female group consisted of individuals with XX chromosomes and the male group with XY chromosomes. The authors indicate that gender could have a cultural component independent of sex, something their data cannot determine. In this sense, this cultural or social character of gender could affect gene expression in the brain throughout the individual's life, and they explicitly recognize that the sex-related differences found in their study could have a component that was affected by socialization and experience, such critical aspects of being human.