Biology subjects

Khetan, M.

Publications and source records attributed to Khetan, M..

3 recordsLinked to original sources

bioRxiv2025

Oestradiol and Progesterone Variability in Adolescent Females: Associations with Brain Structure and Mental Health Problems

ObjectiveAdolescent females are at increased risk for adverse mental health problems, and puberty is thought to be a critical factor. Pubertal onset involves substantial variability in oestradiol (E2) and progesterone (P4), yet the impact of these hormone dynamics remains unclear. We investigated whether within-individual E2 and P4 variability across one month relates to brain structure and mental health problems in adolescent females. MethodsParticipants were 147 females (11-17 years) from the community-based, cross-sectional Puberty and NeuroDevelopment in Adolescents (PANDA) study in Australia. Salivary E2 and P4 were collected weekly for one month, with variability indexed as within-subject standard deviation. Structural MRI was acquired on the final sampling day. Mental health problems were assessed via self- and parent-report. Linear regression and mediation analyses tested associations between hormone variability, brain structure, and mental health, adjusting for demographics. ResultsGreater P4 variability was associated with smaller left thalamus volume (Cohens d = -0.26, pFDR = 0.031). Higher E2 variability was associated with fewer anxiety (d = -0.170, pFDR = 0.043) and depressive symptoms (d = -0.179, pFDR = 0.036), lower emotion dysregulation (d = -0.179, pFDR = 0.036), and smaller right hippocampus volume in pre-menarchal adolescents (d = -0.192, p = 0.02). Weekly reductions in E2 predicted lower positive affect (d = 0.084, p = 0.048). ConclusionThese findings indicate that hormone variability may meaningfully shape brain and behavioural development in adolescent girls differently from hormone-related transitions in adulthood. Larger, replicable, and longer-term studies are needed to confirm these patterns. Oestradiol and Progesterone Variability in Adolescent Females: Associations with Brain Structure and Mental Health Problems. Muskan Khetan 1, Ye Ella Tian 2, Nandita Vijayakumar 3,4, Sarah Whittle 1,4 O_LICentre for Youth Mental Health, University of Melbourne, Australia C_LIO_LIDepartment of Psychiatry, University of Melbourne, Australia C_LIO_LIMurdoch Childrens Research Institute, Australia C_LIO_LISchool of Psychology, Deakin University, Australia C_LI

neuroscience↗

bioRxiv2025

Linking Oestradiol (E2) Timing and Tempo, Brain Development, and Mental Health in Adolescent Females

Background: Earlier timing and faster tempo of puberty have been associated with altered brain development and increased mental health symptoms in adolescents, particularly females. However, the role of oestradiol (E2) in these associations is unclear. Methods: Using longitudinal data from the US-based Adolescent Brain Cognitive Development Study SM (ABCD Study (R), we investigated whether, in females (N ~ 3k), E2 timing (at age 10) and tempo (rate of change from age 10 to 12) were prospectively associated with mental health symptoms at age 13 via structural brain development from age 10 to 12. Linear mixed-effects models and Bayesian mediation models were fitted to investigate the aims of the study. Results: Findings showed that E2 timing was not associated with mental health symptoms. However, earlier E2 timing was associated with a greater reduction in total cortical volume, total surface area, and surface area in the superior and middle temporal cortex over time. Further, a faster E2 tempo was associated with an increase in mental health symptoms, and this association was mediated by a faster reduction in total cortical volume and total surface area over time. Conclusion: Findings suggest that earlier E2 timing and faster E2 tempo contribute to accelerated development of gray matter structure in adolescent females, and for E2 tempo, such associated brain changes may partly contribute to increased mental health risk.

neuroscience↗

bioRxiv2024

Pubertal hormones and the early adolescent female brain: a multimodality brain MRI study

Puberty is a critical developmental process that is associated with changes in 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 DevelopmentSM (ABCD(R)) 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, were among the most 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.

neuroscience↗