Regional sex differences in human cortical anatomy vary in their morphometric bases and overlap with sex chromosomal and gonadal influences
Abstract Humans show reproducible sex differences in regional cortical volume (CV), but it remains unclear how these relate to the two biologically dissociable determinants of CV – surface area (SA) and cortical thickness (CT) – or to potentially causal sex chromosomal and gonadal effects. Here, we analyze neuroimaging data in two independent human cohorts ( N = 1754) to identify and interrelate highly reproducible sex differences in regional CV, SA and CT – as well as their alignment with distinct functional networks and histomolecular signatures. Integrating neuroimaging data from clinical cohorts with sex chromosome aneuploidy and isolated gonadotropin-releasing hormone deficiency (N = 313) establishes that regions of sex-biased cortical anatomy are enriched for congruent effects of X-chromosome dosage (e.g., primary sensory and insular cortices) and gonadal hormones (e.g., dorsal parietal regions and angular gyrus). This work refines maps of sex-biased human cortical organization and helps to narrow hypotheses regarding their potential genetic and endocrine causes.
Authors
- François Lalonde (ORCID: https://orcid.org/0000-0003-4250-6088)
- M. Mallar Chakravarty (ORCID: https://orcid.org/0000-0002-0759-5508)
- Angela Delaney (ORCID: https://orcid.org/0000-0002-0632-6365)
- Elisa Guma (ORCID: https://orcid.org/0000-0003-4651-8529)
- Elizabeth Levitis (ORCID: https://orcid.org/0000-0003-0905-6687)
- Armin Raznahan (ORCID: https://orcid.org/0000-0002-5622-1190)
- Konrad Wagstyl (ORCID: https://orcid.org/0000-0003-3439-5808)
- Rebecca Shafee (ORCID: https://orcid.org/0009-0007-1897-3272)
- Alex DeCasien
- Siyuan Liu (ORCID: https://orcid.org/0000-0003-3661-6248)
- Hyo Min Lee (ORCID: https://orcid.org/0000-0003-0808-4985)
- Gabrielle Dugan (ORCID: https://orcid.org/0009-0006-4945-7003)
- Liv Clasen
- Jason P. Lerch
Institutions
- St. Jude Children's Research Hospital (US)
- Children's Hospital of Philadelphia (US)
- King's College London (GB)
- University of Toronto (CA)
- Great Ormond Street Hospital (GB)
- Hospital for Sick Children (CA)
- University of Oxford (GB)
- Massachusetts General Hospital (US)
- Wellcome Centre for Integrative Neuroimaging (GB)
- National Institute on Aging (US)
- National Institute of Mental Health (US)
- University College London (GB)
- McGill University (CA)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-06-13
- DOI
- https://doi.org/10.1038/s41467-026-74274-8
- Primary Topic
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Type
- article
- Field-Weighted Citation Impact
- 0.00