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. 
