# An RDoC Approach to Perinatal Affective Disorders: The Role of Neuroactive Steroids and Potential Threat

> **NIH NIH F31** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2022 · $41,800

## Abstract

PROJECT SUMMARY / ABSTRACT
Perinatal depression (PND) affects 6.5%-12.9% of mothers, with comorbid perinatal anxiety (PNA) occurring in
as many as 50% of cases. In low-income women of color, rates of these perinatal affective disorders (PNAD)
are even higher. PNAD are associated with adverse effects on both maternal and infant health and can contribute
to pre-term birth and low birth weight. It is important to further our understanding of PNAD to more efficaciously
identify and treat women, especially in at-risk populations. We must also address the considerable heterogeneity
of mental health symptoms and recognize the potential variations in pathogenesis and symptom profiles from
patient to patient. To our knowledge, despite this heterogeneity, studies to date have investigated biomarkers of
PNAD almost exclusively in relation to diagnoses rather than symptom phenotypes. The Research Domain
Criteria (RDoC) framework is a tool for applying new, multi-level mechanistic investigational approaches to
mental health, integrating self-report, behavioral, physiological and biological measures. RDoC tools have not
yet been applied to identify transdiagnostic phenotypes of PNAD and their neural basis. Neuroactive steroid
metabolites of progesterone fluctuate drastically during pregnancy and have been implicated in the pathogenesis
of PNAD. These neuroactive steroids alter the neural circuitry (i.e., inhibitory GABAA receptor) modulating certain
RDoC phenotypes, particularly potential threat, or responses to potentially aversive situations. Preliminary data
show potential threat to be an RDoC phenotype common in PNAD, and neuroactive steroids to relate to PNAD.
The next step is to link potential threat directly to neuroactive steroids, and to extend research to other
metabolites of progesterone, particularly early in pregnancy when rates of PNAD are highest in women of color.
The research goal of this proposal is to examine neuroactive steroid synthesis in relation to self-report and
physiological measures of potential threat as well as PNAD symptoms in early pregnancy in low-income women
of color. The specific aims are to (1) investigate acute increases in NAS synthesis as a mechanism of potential
threat in early pregnancy; (2) investigate the association of NAS synthesis with depression and anxiety
symptoms in early pregnancy, and whether potential threat mediates these associations; and (3) investigate the
acoustic startle response as a physiological index of potential threat and GABAA receptor sensitivity to NAS
during pregnancy. The training goals are to (1) develop a theoretical understanding of the RDoC framework
and apply the framework to the study of perinatal mental health phenotypes; (2) acquire training in processing
and analysis of neuroactive steroids, and gain knowledge of their association with PNAD; and (3) develop a
detailed understanding of female reproductive physiology and endocrinology, and relate this to perinatal affective
disorders...

## Key facts

- **NIH application ID:** 10464233
- **Project number:** 1F31MH130077-01
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Elizabeth Wenzel
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $41,800
- **Award type:** 1
- **Project period:** 2022-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10464233

## Citation

> US National Institutes of Health, RePORTER application 10464233, An RDoC Approach to Perinatal Affective Disorders: The Role of Neuroactive Steroids and Potential Threat (1F31MH130077-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10464233. Licensed CC0.

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