About this trial
Pubertal transition leads to enduring neuroendocrine changes along with changes in the epigenome. The prevalence of psychiatric disorders significantly increases in females compared to males after puberty. There is likely to be an interaction between epigenetics, hormones and neurophysiological processes during puberty, leading to the increased prevalence of mental disorders in females. This study aims to shed light on these interactions underlying the emerging sex differences after puberty. Specifically, it seeks to investigate the epigenetic modifications and subsequent changes in gene expression during the pubertal transition and their association with negative emotionality (e.g., acute stress response and depressive symptoms) at molecular, neuronal, subjective and physiological levels.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
healthy girls
aged between 8-10 and having pubertal stage 1 or between 15-17 and having pubertal stage 5
normal body mass index according to age (between 5th and 85th percentile)
non-smoking
Disqualifiers
neurological or psychiatric disease
medical problems such as hormonal, metabolic, developmental or chronic diseases (e.g., congenital disorders, precocious puberty, polycystic ovarian syndrome, diabetes or congestive heart failure)
any kind of hormonal, pharmacological or psychotropic treatment in the last three months
engaging in competitive/extreme sports
Trial population
Pubescent girls between 8 and 17 years of age living and schooling in Tübingen and surrounding area
Trial design
Cohort
Cross-sectional
Treatments tested in this trial
Stress
BehavioralMontreal Imaging Stress Task is a stress paradigm in the scanner to examine neuronal correlates of acute psychosocial stress.
Treatment groups
Trial outcomes
Primary outcomes
DNA methylation differences between pre- and post-pubertal girls in candidate genes
DNA methylation (DNAm) leves in genes involved in estrogen signaling and neuronal estrogen responsive genes in blood and saliva
Correlation between DNA methylation and neuronal activity during acute stress
Neuronal activity during acute stress is determined by the contrast differences between stress and control conditions assessed with task-based fMRI, Montreal Imaging Stress Task (MIST). The correlation between neuronal activity and DNA methylation. Comparing pre- and post-pubescent girls.
The mediating role of sex steroids in DNA methlation and negative emotionality
The mediating effect of estradiol, progesterone, testosterone and allopregnanolone levels in blood on the correlation between DNA methylation and indicators of negative emotionality (e.g., neuronal activity during stress (MIST task) and mood symptoms). Comparing pre- and post-pubescent girls
Secondary outcomes
Correlation between DNA methylation and gene expression in candidate genes
The expression levels of genes involved in estrogen signaling and neuronal estrogen responsive genes in blood and saliva with RT-PCR. Correlation between DNA methlaytion and expression.
Correlation between DNA methylation and HPA-axis response
Cortisol levels from saliva samples collected before and after MIST. Correlation between area under the curve (AUC) for cortisol and DNA methylation. Is there a mediating role of DNA methylation on the correlation between HPA-axis reactivity and negative emotionality (e.g., internalizing symptoms and stress processing)? Comparing pre- and post-pubescent girls.
Correlation between DNA methylation and subjective stress response
Correlation between emotional ratings and stress levels assessed with each saliva sample before and after MIST and DNA methylation. Emotional ratings are based on self-assessment mannikin (SAM) which is a non-verbal pictorial tool. Stress levels evaluated with a stress thermometer using a scale of 1-10; 1 indicating not at all, 10 very strong. Is there a mediating effect of DNA methylation on the correlation between subjective stress response and negative emotionality (e.g., internalizing symptoms and stress processing). Comparing pre-and post-pubertal girls
Correlation between DNA methylation and phsiological stress response
Correlation between HR, HRV and skin conductance changes during stress task (MIST) and DNA methylation. The interaction between physiological acute stress response and DNA methylation in relation to negative emotionality (e.g., internalizing symptoms and stress processing). Comparing pre-and post-pubertal girls
Sponsors and contacts
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International Research Training Group 2804
Lead sponsor
University Hospital Tuebingen
Collaborator
Uppsala University
Collaborator
German Research Foundation
Collaborator