Negative Emotionality and Epigenetics During Puberty

NCT06690866 | Recruiting

• 1 other identifier: IRTG_P01
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Puberty; Healthy; Stress

Keywords

Stress reactivity; DNA methylation; fMRI

Outcome Measures

Primary Outcomes (3)

• 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

  Measured once after MRI measurement (approximately 30 minutes).

• 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.

  Measured once: 3 runs of MIST lasting 20 minutes in total.

• 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

  Measured once for each part: 20 minutes for MIST, 30 minutes for blood and saliva collection, and 1 hour for questionnaires

Secondary Outcomes (6)

• Correlation between DNA methylation and gene expression in candidate genes

  Measured once after MRI measurement (approximately 30 minutes)

• Correlation between DNA methylation and HPA-axis response

  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

  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

  Measured once: 20 minutes for phsiological data during MRI measurement

• Correlation between DNA methylation and functional connectivity

  Measured once with resting-state functional MRI, approximately 10 mintes

Study Arms (2)

Pre-pubertal girls (children)

8-10 years of girls having pubertal stage 1

Behavioral: Stress

Post-pubertal girls (adolescents)

15-17 years of girls having pubertal stage 5

Behavioral: Stress

Interventions

Stress BEHAVIORAL

Montreal Imaging Stress Task is a stress paradigm in the scanner to examine neuronal correlates of acute psychosocial stress.

Post-pubertal girls (adolescents); Pre-pubertal girls (children)

Eligibility Criteria

• Age: 8 Years - 17 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Pubescent girls between 8 and 17 years of age living and schooling in Tübingen and surrounding area

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• International Research Training Group 2804: lead
• University Hospital Tuebingen: collaborator
• Uppsala University: collaborator
• German Research Foundation: collaborator

Study Sites (1)

University of Tuebingen; Department of Psychiatry & Psychotherapy; Tuebingen

Tübingen, Baden-Wurttemberg, 72076, Germany

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood, saliva and hair

Study Officials

• Vanessa Nieratschker, Prof.

  University Hospital Tuebingen

  PRINCIPAL INVESTIGATOR

• Mirac Nur Musaoglu, MD

  University Hospital Tuebingen

  STUDY DIRECTOR

Central Study Contacts

Vanessa Nieratschker, Prof. Dr.

CONTACT

+497071-2985523; vanessa.nieratschker@med.uni-tuebingen.de

Birgit Derntl, Prof. Dr.

CONTACT

+497071 29-85437; birgit.derntl@med.uni-tuebingen.de

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2024
• First Posted: November 15, 2024
• Study Start: March 26, 2024
• Primary Completion: December 1, 2025
• Study Completion: April 1, 2026
• Last Updated: November 15, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ANALYTIC CODE
• Time Frame: Data will become available after an embargo period of 12 months after completion of the study.
• Access Criteria: Until the data is publicly available, researchers may contact the lead PI to gain access.

Locations

DE (1)