Negative Emotionality and Epigenetics During Puberty

NCT ID: NCT06690866

Last Updated: 2024-11-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

100 participants

Study Classification

OBSERVATIONAL

Study Start Date

2024-03-26

Study Completion Date

2026-04-30

Brief Summary

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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

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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.

Conditions

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Puberty Healthy Stress

Study Design

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Observational Model Type

COHORT

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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Pre-pubertal girls (children)

8-10 years of girls having pubertal stage 1

Stress

Intervention Type BEHAVIORAL

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

Post-pubertal girls (adolescents)

15-17 years of girls having pubertal stage 5

Stress

Intervention Type BEHAVIORAL

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

Interventions

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Stress

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

Intervention Type BEHAVIORAL

Eligibility Criteria

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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


* 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
Minimum Eligible Age

8 Years

Maximum Eligible Age

17 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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University Hospital Tuebingen

OTHER

Sponsor Role collaborator

Uppsala University

OTHER

Sponsor Role collaborator

German Research Foundation

OTHER

Sponsor Role collaborator

International Research Training Group 2804

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Vanessa Nieratschker, Prof.

Role: PRINCIPAL_INVESTIGATOR

University Hospital Tuebingen

Mirac Nur Musaoglu, MD

Role: STUDY_DIRECTOR

University Hospital Tuebingen

Locations

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University of Tuebingen; Department of Psychiatry & Psychotherapy; Tuebingen

Tübingen, Baden-Wurttemberg, Germany

Site Status RECRUITING

Countries

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Germany

Central Contacts

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Vanessa Nieratschker, Prof. Dr.

Role: CONTACT

+497071-2985523

Birgit Derntl, Prof. Dr.

Role: CONTACT

+497071 29-85437

Facility Contacts

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Vanessa Nieratschker, Prof. Dr.

Role: primary

+497071 29-85523

Mirac Nur Musaoglu, MD

Role: backup

Vanessa Nieratschker, Prof. Dr.

Role: backup

Other Identifiers

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IRTG_P01

Identifier Type: -

Identifier Source: org_study_id

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