Menarche onset is an inflection point for mental health and brain development
Menarche is a normative milestone of female puberty, yet its role in adolescent mental health and brain development remains poorly understood. Using longitudinal data from 5,016 females (7 annual visits, ages 10-16 years) in the Adolescent Brain Cognitive Development Study, we found that menarche onset functions as an inflection point for the development of internalizing symptoms and gross brain morphometry. The onset of menarche, largely independent of timing and socio-environmental factors, preceded a significant spike in internalizing symptoms, while altering the rate of ongoing structural brain development. Following menarche onset, individuals with faster declines in gray matter volume and surface area also had heightened internalizing symptoms. These findings suggest that menarche is not only a reproductive milestone but a neuroendocrine driver of adolescent brain and mental health trajectories. This normative and easily identifiable marker could define a critical window for mental health screenings with greater precision than current age-based guidelines.
Authors
- Holly Sullivan‐Toole (ORCID: https://orcid.org/0000-0001-9617-9276)
- Arielle S. Keller (ORCID: https://orcid.org/0000-0003-4708-1672)
- Damien A. Fair (ORCID: https://orcid.org/0000-0001-8602-393X)
- Brenden Tervo‐Clemmens (ORCID: https://orcid.org/0000-0002-9557-1126)
- Emily Goard Jacobs (ORCID: https://orcid.org/0000-0003-0001-5096)
- John France (ORCID: https://orcid.org/0000-0002-7749-7567)
- Martin Gell (ORCID: https://orcid.org/0000-0002-3407-3393)
- Ran Barzilay (ORCID: https://orcid.org/0000-0002-3247-2331)
- Carina Heller (ORCID: https://orcid.org/0000-0001-6187-6987)
- Sanju Koirala (ORCID: https://orcid.org/0000-0001-8844-4586)
- Bart Larsen
- Adriene M. Beltz
- Tyler M. Moore
- Ka I Ip
Institutions
- University of Minnesota (US)
- Children's Hospital of Philadelphia (US)
- University of Connecticut (US)
- University of California, Santa Barbara (US)
- University of Michigan (US)
- Jena University Hospital (DE)
- University of Pennsylvania (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-04-14
- DOI
- https://doi.org/10.64898/2026.04.13.718198
- Primary Topic
- Hypothalamic control of reproductive hormones
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Brain and Behavior Research Foundation
- Deutsche Forschungsgemeinschaft
- National Institutes of Health
- National Institute of Mental Health
- Common Fund