Oestradiol Timing and Tempo as Predictors of Brain Development and Mental Health in Adolescent Girls
Poster No:
990
Submission Type:
Abstract Submission
Authors:
Muskan Khetan1, Nandita Vijayakumar2, Ye Ella Tian1, Sarah Whittle3
Institutions:
1University of Melbourne, Melbourne, Victoria, 2Deakin University, Melbourne, VIC, 3Unversity of Melbourne, Melbourne, Victoria
First Author:
Co-Author(s):
Introduction:
Earlier pubertal timing (onset of puberty) and faster pubertal tempo (progression through puberty) have been associated with mental health problems in female adolescents (Deardorff et al., 2021; Keenan et al., 2014; Marceau et al., 2011). However, prior studies have investigated physical pubertal indicators, and it is unclear how the timing and tempo of pubertal hormones, particularly oestradiol (E2), confer risk. This study explored how the timing and tempo of E2 exposure predict brain development and, in turn, mental health symptoms in adolescent females.
Methods:
We utilised E2 and pre-processed neuroimaging data from baseline and Wave 2 (two years later), as well as mental health symptom data from Wave 3 (three years later), drawn from the U.S.-based Adolescent Brain Cognitive Development Study (N ~ 3,000 females; aged 9–13 years). Mental health symptoms were assessed using the adolescent-reported Brief Problem Monitor (BPM; Achenbach et al., 2011), which includes three subscales: attention, internalising, and externalising, in addition to a "total problems" score. Neuroimaging data were processed using FreeSurfer v7.1.1, where cortical regions were parcellated with the Desikan atlas (Dale et al., 1999; Fischl et al., 1999b) and subcortical regions were parcellated using FreeSurfer's subcortical segmentation (Fischl et al., 2002). Whole-brain white matter (WM) fiber tracts were parcellated using the AtlasTrack atlas (Hagler et al., 2009).
E2 timing was calculated using residuals from a linear model predicting E2 levels based on age, while E2 tempo was defined as the rate of change in E2 over two years. Brain measures included cortical structure (thickness, volume, surface area, sulcal depth), subcortical volume, and white matter microstructure across various brain regions and tracts. Further, Linear mixed-effects models (R-package "nlme") were employed to assess how E2 timing and tempo predicted the rate of change in brain structure (cortical, subcortical, and white matter microstructure). For significant results, mediation analyses were performed using Bayesian methods (R-package "brms") to evaluate whether the rate of change in brain structure mediated the relationship between E2 timing/tempo and mental health symptoms (see Figure 1).
E2 timing was calculated using residuals from a linear model predicting E2 levels based on age, while E2 tempo was defined as the rate of change in E2 over two years. Brain measures included cortical structure (thickness, volume, surface area, sulcal depth), subcortical volume, and white matter microstructure across various brain regions and tracts. Further, Linear mixed-effects models (R-package "nlme") were employed to assess how E2 timing and tempo predicted the rate of change in brain structure (cortical, subcortical, and white matter microstructure). For significant results, mediation analyses were performed using Bayesian methods (R-package "brms") to evaluate whether the rate of change in brain structure mediated the relationship between E2 timing/tempo and mental health symptoms (see Figure 1).
Results:
E2 timing was significantly negatively associated with the developmental change in total cortical volume (β = -26.17, p = 0.018), total surface area (β = -6.57, p = 0.016), and surface area in the middle temporal cortex (β = -0.36, pFDR = 0.015). Faster E2 tempo was significantly negatively associated with a developmental change in total cortical volume (β = -1236.27, p = 0.004) and total surface area (β = -242.28, p = 0.027). That is, earlier E2 timing and a faster rate of change in E2 levels were associated with a greater reduction in structural measures over time. In addition, a faster E2 tempo influenced an increase in total mental health symptoms indirectly via reduced cortical volume (β = 0.524, CI95 = 0.043, 1.354).
Conclusions:
Findings suggest that earlier E2 timing and faster tempo are linked to accelerated cortical structure development in adolescent females, with faster tempo indirectly predicting higher mental health symptoms through its impact on these brain structures. These findings align with prior research, suggesting distinct brain development patterns in those at increased risk for mental health issues (Frodl and Skokauskas, 2012).
Impact statement: Findings from this study indicate an influence of early increases in oestradiol levels on brain development, which in turn impacts mental health in female adolescents. The results suggest that mental health interventions for adolescent girls could benefit from considering both the timing and speed of pubertal development, potentially providing early support to those at risk.
Impact statement: Findings from this study indicate an influence of early increases in oestradiol levels on brain development, which in turn impacts mental health in female adolescents. The results suggest that mental health interventions for adolescent girls could benefit from considering both the timing and speed of pubertal development, potentially providing early support to those at risk.
Lifespan Development:
Early life, Adolescence, Aging 1
Modeling and Analysis Methods:
Bayesian Modeling 2
Keywords:
Development
MRI
STRUCTURAL MRI
Structures
White Matter
1|2Indicates the priority used for review
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Provide references using APA citation style.
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