# Defining the Neuropathophysiological Mechanisms Linking Ovarian Hormone Variability with Depression Risk in Peripubertal Girls

> **NIH NIH K01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $158,381

## Abstract

PROJECT SUMMARY/ABSTRACT
The pubertal transition (PT) is a critical developmental window characterized by pronounced reproductive
hormone variability, extensive refinement of frontal neural networks, and substantially increased risk for
depression in girls. Rejection sensitivity (RejSen) is a strong proximal risk factor for depression and a
developmentally relevant psychological construct in adolescent girls. Adolescent girls experience stronger
emotional and physiological reactivity to interpersonal stress exposure (IntStressExp), possibly contributing to
their disproportionate risk for affective illness. This sex disparity, first emerging at puberty and continuing
throughout the reproductive lifespan, implicates ovarian hormones (e.g., estradiol, E2) in the vulnerability to
psychopathology. The proposed K01 project will employ a multimodal, dimensional approach to investigating the
pathophysiological role of ovarian hormones in regulating frontal cognitive control, cortisol stress reactivity and
RejSen in PT and post-PT girls. A secondary objective is to define the neurophysiological mechanisms that make
the PT a unique window of vulnerability for psychopathology in adolescent girls. Characterizing endogenous E2
variability during the PT and potential mediators of the E2 pathway to psychopathology represents an
understudied and significant area of research, and is consistent with NIMH’s strategic objective of defining the
trajectory of mental illness. 120 adolescent girls (60 ages 11-14, ≤1 year post-menarche and 60 ages 15-18, >2
years post-menarche) will provide daily salivary E2 measurements and RejSen ratings for 1 month, and
laboratory testing involving cortisol stress reactivity and EEG measures of cognitive control to test the hypothesis
that E2 variability during the PT predicts RejSen as preliminary data has shown (Aim 1), frontal cognitive control
(Aim 2), and cortisol stress reactivity (Aim 3), especially in girls with greater IntStressExp. Mentors were selected
given their documented success and experience as mentors, and expertise in the following areas: reproductive
and stress neuroendocrinology (Susan Girdler, Ph.D., primary mentor), interpersonal stress factors
contributing to female adolescent depression (Mitch Prinstein, Ph.D.), endocrinology of puberty (Ali Calikoglu,
M.D.), and multilevel statistical analyses to investigate state changes in hormones and affective symptoms
(Daniel Bauer, Ph.D.). Career Goal: I am committed to an independently funded research career focused on
investigating ovarian hormone flux in the pathophysiology relevant to the emergence of depression in girls during
the PT. My long-term objective is to construct a comprehensive model of depression susceptibility in peripubertal
girls to inform targeted intervention strategies for the early detection and prevention of depression. Career
Development: The proposed study complements my previous research experience and knowledge with new
technical, profession...

## Key facts

- **NIH application ID:** 10055232
- **Project number:** 1K01MH121575-01A1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Elizabeth Helen Andersen
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $158,381
- **Award type:** 1
- **Project period:** 2020-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10055232

## Citation

> US National Institutes of Health, RePORTER application 10055232, Defining the Neuropathophysiological Mechanisms Linking Ovarian Hormone Variability with Depression Risk in Peripubertal Girls (1K01MH121575-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10055232. Licensed CC0.

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