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Pubertal Hormones and the Early Adolescent Female Brain: A Multimodality Brain MRI Study.

February 1, 2026pubmed logopapers

Authors

Khetan M,Vijayakumar N,Tian YE,Herting MM,O'Connell M,Seal M,Whittle S

Affiliations (8)

  • Centre for Youth Mental Health, The University of Melbourne, Melbourne, Victoria, Australia.
  • Orygen, The National Centre of Excellence in Youth Mental Health, Melbourne, Victoria, Australia.
  • Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
  • Department of Population and Public Health Sciences, University of Southern California, California, Los Angeles, USA.
  • School of Psychology, Deakin University, Sydney, Victoria, Australia.
  • Department of Psychiatry, University of Melbourne, Melbourne, Victoria, Australia.
  • Department of Paediatrics, The University of Melbourne, Melbourne, Victoria, Australia.
  • Department of Endocrinology & Diabetes, The Royal Children's Hospital, Melbourne, Victoria, Australia.

Abstract

Puberty is a critical developmental process that is associated with changes in pubertal (or steroid) hormone levels, which are believed to influence adolescent behaviour via their effects on the developing brain. So far, there are limited and inconsistent findings regarding the relationship between steroid hormones and brain structure and function in adolescent females, with many existing studies employing small sample sizes. Thus, in this study, we explored the association between oestradiol (E2), testosterone (Tes), and dehydroepiandrosterone (DHEA) and brain structure (gray matter volume, sulcal depth, cortical thickness, and white matter microstructure) and function (resting-state connectivity, emotional n-back task-related function) in 3024 adolescent females (age 8.92-13.33 years, mean age (SD) = 10.37 (0.94) years) from the Adolescent Brain Cognitive Development<sup>SM</sup> (ABCD) Study. We used elastic-net regression with cross-validation to investigate associations between hormones and brain phenotypes derived from multiple imaging modalities. We found that structural brain features, including cortical thickness, sulcal depth, and white matter microstructure, and resting state connectivity between cortical networks and subcortical regions, were important features associated with hormones. E2 was most strongly associated with prefrontal and premotor regions involved in working memory and emotion processing, while Tes and DHEA were most strongly associated with parietal and occipital regions involved in visuospatial functioning. All three hormones were also associated with prefrontal, temporoparietal junction, and insula cortices. Thus, using an advanced methodological approach, this study suggests both unique and overlapping neural correlates of pubertal hormones in adolescent females and sheds light on the mechanisms by which puberty influences adolescent development and behaviour.

Topics

EstradiolDehydroepiandrosteronePubertyTestosteroneAdolescent DevelopmentBrainConnectomeCerebral CortexJournal Article

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