Neurophysiology, Estrogen, and Stress Exposure in the Emergence of Depression in Adolescent Girls

Stress Clinical Trial

— EVOLVE  

Official title:

Ovarian Hormone Variability and Mood Symptoms in Girls During the Pubertal Transition

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03450135
• Other study ID #: 17-2173
• Secondary ID: 2KR961702
• Status: Completed
• Start date: February 25, 2018
• Est. completion date: June 30, 2020

Study information

• Verified date: November 2020
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The prevalence of adolescent depression is steadily rising in the U.S., especially among adolescent girls. Currently 20% of adolescent girls experience major depression compared with 6% of boys (National Institute of Mental Health, 2016). The profound gender disparity in depression that emerges at puberty, but not before, implicates a role of ovarian steroid hormones in promoting affective (mood) symptoms in adolescent girls. In addition to dramatic physical maturation and a rapidly changing reproductive hormone environment at puberty, adolescence is also a time of exposure to substantial psychosocial stress, particularly in girls. It is well documented that stress interferes with the maturation of neurodevelopmental trajectories and is a critical precipitating factor in the pathway to psychopathology. However, the neuropathophysiological mechanisms linking stress exposure and sensitivity to ovarian hormone fluctuations at puberty to the onset and maintenance of depression symptoms in adolescence have yet to be elucidated, and is the purpose of this research.

Description:

Framed within a diathesis-stress model of disease, the primary objective of this research is to determine a pathophysiological role of estradiol (E2) variability in the context of severe psychosocial stress exposure in regulating neurophysiological correlates of affective state change in girls (ages 11-14) during the pubertal transition (i.e., Tanner developmental stages 3 or 4). The rationale for examining E2 variability as a diathesis for mood impairment is twofold. First, sensitivity to hormonal flux during specific reproductive events has been shown to trigger affective symptoms in susceptible women, and second, E2 is a powerful neuroregulator of neural networks implicated in depression.

55 peripubertal girls undergoing a healthy pubertal transition will be recruited for the study. Over an 8-week period, depression symptoms (Center for Epidemiological Studies Depression Scale for Children (CES-DC)), anxiety (State Trait Anxiety Inventory (STAI-C)), and perceived stress (perceived stress scale (PSS)), and salivary E2 measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) will be assessed on a weekly basis. An electroencephalogram (EEG) during an emotional go/no-go task will be performed after the 8-week collection period to probe neurophysiological correlates of maturing fronto-limbic circuitry and assess key domains of cognitive and emotional processing impacted by the hormonal milieu. At the follow-up visit, an acute psychosocial stressor (Trier Social Stress Test) will be administered to examine cortisol and autonomic stress reactivity. The central hypothesis of the proposed research is that the amplitude and synchrony of frontal neural oscillations evoked during the cognitive-affective processing paradigm, and cortisol reactivity to the psychosocial stressor will partially mediate the relationship between greater E2 variability and elevated depression symptoms in peripubertal girls, and this relationship will be particularly strong in girls who have experienced recent (within six months) psychosocial stress.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: June 30, 2020
• Est. primary completion date: June 30, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 11 Years to 14 Years

Eligibility

Inclusion Criteria:

• Female, 11 to 14 years of age

• Meet Tanner developmental stage criteria (as indicated by self-report and pictorial scales of breast and pubic hair development) for pubertal stages 3 or 4

• Must be undergoing a healthy pubertal transition, pre-or-post menarche (within 15 months of menarche, with cycle irregularity)

• Girls must be able to read at a 4th-grade reading level

Exclusion Criteria:

• Current suicidal intent (based off Columbia-Suicide Severity rating scale)

• A history or current diagnosis of bipolar disorder or psychosis

• Currently on any prescription medications

Related Conditions & MeSH terms

• Adolescent Development
• Affective Symptoms
• Emotional Disturbances
• Stress

Intervention

Behavioral:
• Trier Social Stress Test
Participants will perform an acute psychosocial stress manipulation (Trier Social Stress Test) involving a speech task and challenging mental arithmetic.
• Emotional go/no-go task
Participants will perform an emotional go/no-go paradigm to examine electrophysiological (EEG) correlates of cognitive and affective processing.

Locations

Country	Name	City	State
United States	University of North Carolina, SHARRP Lab	Chapel Hill	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	North Carolina Translational and Clinical Sciences Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Average mood symptom score from Mood and Feelings Questionnaire	The MFQ consists of 33 descriptive phrases regarding how the subject has been feeling or acting recently (past two weeks) on a 3-point force-choice Likert-type response scales (most of the time, sometimes, or not at all). Greater scores reflect greater symptom severity.	Week 10
Secondary	Theta (4-8 Hz) oscillatory activity elicited during an affective task	Theta oscillations (synchronization of power and phase with respect to stimulus presentation) will be assessed during an emotional go/no-go paradigm to reflect cognitive and emotional processing.	Week 10
Secondary	Salivary cortisol response to an acute psychosocial stress manipulation	The stress hormone cortisol will be assessed at rest and in response to the Trier Social Stress Test at baseline (enrollment).	Week 10