Negative Emotionality and Epigenetics During Puberty
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Stress.
- Who it may be relevant to
- Registry conditions: Puberty, Healthy, Stress. Basic parameters: 8 years — 17 years · Female.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Germany
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
Negative Emotionality in Relation to Epigenetics of Estrogen Signaling During Puberty
Overview
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.
Detailed description
In order to investigate epigenetic and neuroimaging correlates of negative emotionality in pubertal girls, the study employs a cross-sectional design, enrolling 50 pre-pubescent girls (8-10 years) and 50 post-pubescent girls (15-17 years) as healthy participants. Comprehensive data will be collected using self- and parent-report questionnaires on pubertal status, prenatal complications, adverse life events, stress and coping mechanisms, mood and anxiety symptoms, gender identity, and reproductive health. To delve into the neuronal correlates of stress, participants will undergo (f)MRI and MIST. Additionally, physiological stress responses will be assessed through heart rate and skin conductance measurements. Participants will provide blood, saliva, and hair samples for hormone, methylation and expression analysis. DNA methylation analysis will be performed on whole blood and saliva samples using pyrosequencing, focusing on genes that are responsive to estrogen and genes involved in estrogen signaling, based on the previous literature reporting an overrepresentation of estrogen-responsive genes among the differentially methylated sites across the entire genome in girls during puberty. The effects of methylation on gene expression will be measured using reverse transcription real-time PCR. Cortisol levels will be assessed from saliva collected six times during MIST to evaluate the acute stress response and from hair to assess chronic stress. Sex steroids such as estrogen and progesterone from blood will be analyzed using LC-MS/MS. The study aims to provide insights into the intricate relationship between epigenetic modifications, gene expression and negative emotionality (e.g., stress reactivity and internalizing symptoms) during puberty in girls.
Interventions
- Behavioral Stress
Montreal Imaging Stress Task is a stress paradigm in the scanner to examine neuronal correlates of acute psychosocial stress.
Primary outcome measures
- DNA methylation differences between pre- and post-pubertal girls in candidate genes [Time frame: Measured once after MRI measurement (approximately 30 minutes).]
- Correlation between DNA methylation and neuronal activity during acute stress [Time frame: Measured once: 3 runs of MIST lasting 20 minutes in total.]
- The mediating role of sex steroids in DNA methlation and negative emotionality [Time frame: Measured once for each part: 20 minutes for MIST, 30 minutes for blood and saliva collection, and 1 hour for questionnaires]
Secondary outcome measures (6)
- Correlation between DNA methylation and gene expression in candidate genes [Time frame: Measured once after MRI measurement (approximately 30 minutes)]
- Correlation between DNA methylation and HPA-axis response [Time frame: Measured six times: 1 hour before MIST(1), just before(1) and after(1) MIST, and three times more in 20-minute intervals after MIST. Each saliva collection lasts approx. 2 minutes.]
- Correlation between DNA methylation and subjective stress response [Time frame: Measured six times: 1 hour before MIST(1), just before(1) and after(1) MIST, and three times more in 20-minute intervals after MIST. Each rating takes approx. 10 minutes.]
- Correlation between DNA methylation and phsiological stress response [Time frame: Measured once: 20 minutes for phsiological data during MRI measurement]
- Correlation between DNA methylation and functional connectivity [Time frame: Measured once with resting-state functional MRI, approximately 10 mintes]
- Correlation between DNA methylation and brain gray matter structure [Time frame: Measured once with MPRAGE MRI, approximately 10 minutes. Analyzed and reported over the course of the study, in average of 1 year]
Eligibility criteria
Inclusion criteria
- 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
- German language fluency
- Attending age-appropriate schools
Exclusion criteria
- 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
Additional exclusion criteria for MRI:
- People with non-removable metal objects on or in the body
- Tattoos (if not MRI-incompatible according to expert guidelines)
- Pathological hearing or increased sensitivity to loud noises
- Claustrophobia
- Surgery less than three months ago
- Moderate or severe head injury
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Observational model
- Cohort
Study locations
Germany · 1 center
- University of Tuebingen; Department of Psychiatry & Psychotherapy; Tuebingen — Tübingen
Identifiers
NCT: NCT06690866 · IRTG_P01