Male brain, female brain: invisible differences that may impact our mental health

By Elodie Vaz | Published on April 23, 2026 | 3 min read


Psychiatric and neurological disorders—from ADHD to schizophrenia, including depression and Alzheimer’s disease—show marked differences depending on biological sex. Men and women, defined respectively by XY and XX chromosomes, are not equal in the face of these conditions, whether in terms of prevalence, age of onset, or progression. While these disparities are often attributed to a mix of biological and social factors, their consistency across cultures and their emergence at key developmental stages suggest a deeper biological basis, possibly linked to gene expression in the brain.  

In this context, Alex DeCasien’s team sought to determine whether sex-related differences exist at the level of brain gene transcription in a study published in Science on April 16. The central hypothesis is that subtle but systematic variations in gene expression may help explain differences in vulnerability to neuropsychiatric disorders between men and women.  

A deep dive into the brain, cell by cell

The researchers conducted a high-resolution analysis using single-nucleus RNA sequencing (snRNA-seq), a technique that allows gene expression to be examined cell by cell. The study is based on brain samples from 30 adults, evenly divided between men and women.  

Six cortical regions were selected: some known to exhibit structural sex differences, others not. This comparative approach aims to distinguish sex-specific molecular variations from those related to brain architecture.  

The results show that biological sex explains only a small fraction of the overall variability in gene expression in the brain. However, the analysis identified more than 3,000 genes with sex-differential expression in at least one cortical region. Among them, 133 genes show consistent effects across different regions and cell types.  

The key role of hormones beyond chromosomes

Unsurprisingly, the most pronounced differences involve genes located on sex chromosomes. However, most of the observed variations involve autosomal genes—those not linked to sex chromosomes—and are primarily regulated by sex steroid hormones. This highlights the potential role of hormones in modulating brain gene activity.  

Many sex-differentiated genes overlap with genetic variants already associated with neuropsychiatric and neurodegenerative disorders. This convergence reinforces the idea that differences in gene expression may contribute to the disparities observed in these conditions.  

In a related perspective, Professors Jessica Tollkuhn and Marc Breedlove urge caution. “DeCasien et al. explicitly acknowledge that the sex differences observed in their study may arise from differences in socialization and experience.” They add: “One could rule out the influence of such social factors if sex differences in gene expression are present before birth, and future studies may address this question.”

Biology or environment: a still-blurred boundary

This study highlights diffuse but robust differences in gene expression in the human brain according to biological sex. Although modest in magnitude, these variations could play a key role in the differing trajectories of neuropsychiatric diseases.  

It also raises major questions: to what extent are these differences innate or shaped by the environment? And above all, how can these findings be integrated into precision medicine that takes biological sex into account? Future research, particularly on prenatal development, will be crucial to disentangle the interplay between biological and social factors in brain health. 





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  About the Author – Elodie Vaz
Health journalist, CFPJ graduate (2023).
Élodie explores the marks diseases leave on bodies and, more broadly, on human life. A registered nurse since 2010, she spent twelve years at patients’ bedsides before exchanging her stethoscope for a notebook. She now investigates the links between environment and health, convinced that the vitality of life cannot be reduced to that of humans alone.