# Relationships between Neuroactive Steroids, GABA and Glutamate MRS and Connectivity of the Default Mode Network in Postpartum Depression

> **NIH NIH R01** · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · 2020 · $551,736

## Abstract

Project Summary
Postpartum depression is one of the most common complications of childbirth. Untreated postpartum depression
can have substantial adverse effects on the well-being of the mother and child, negatively impacting child cog-
nitive, behavioral, and emotional development with lasting consequences. The underlying pathophysiology of
postpartum depression is largely unknown, creating an obstacle to developing improved treatments. The overall
goal of this study is to determine the relationships between GABAergic and glutamatergic neuroactive steroids,
cortical GABA and GLU concentrations and default mode network resting-state functional connectivity in women
with postpartum depression versus healthy postpartum and non-postpartum women. Our central hypothesis is
that high sustained amplitude neuroactive steroid exposure then withdrawal during the pregnancy and the post-
partum period versus the low brief amplitude neuroactive steroid exposure/withdrawal of the menstrual cycle, is
associated with differential cortical GABA and GLU concentrations within the default mode network and their
correlation to network resting state functional connectivity, with further differences between women with and
without postpartum depression. This study is a prospective observational study of 54 healthy peripartum comparison
women and 54 peripartum women with postpartum depression in comparison to a cross-sectional examination of 54
healthy women in the follicular stage of the menstrual cycle. Peripartum mood data and blood specimens will be ob-
tained at 2 antepartum and 2 postpartum study visits. Healthy postpartum comparison women and women with post-
partum depression will undergo a single functional MRI and magnetic resonance spectroscopy scan in the postpartum
period while healthy women in the follicular phase of the menstrual cycle will complete a single study visit including
mood, blood and neuroimaging measures. The study will examine differences in default mode resting state functional
connectivity across groups (Aim 1), differences in GABA and glutamate concentrations across groups (Aim 2), corre-
lations between spectroscopy and resting-state functional connectivity (Aim 3) and explore correlations of spectros-
copy, resting-state functional connectivity, neuroactive steroids and depression in postpartum depression (Exploratory
Aim 1). Finally, half of the women with postpartum depression will complete a second imaging session after successful
postpartum depression treatment (Exploratory Aim 2) to determine GABA, glutamate and resting-state functional con-
nectivity changes associated with treatment. This data can then serve as an objective index against which to predict
response to current pharmacotherapies, identify new postpartum-specific therapeutic targets and measure po-
tential efficacy of newly developed treatments.

## Key facts

- **NIH application ID:** 9800427
- **Project number:** 1R01MH120313-01
- **Recipient organization:** FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
- **Principal Investigator:** Kristina Marie Deligiannidis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $551,736
- **Award type:** 1
- **Project period:** 2020-05-04 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9800427

## Citation

> US National Institutes of Health, RePORTER application 9800427, Relationships between Neuroactive Steroids, GABA and Glutamate MRS and Connectivity of the Default Mode Network in Postpartum Depression (1R01MH120313-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9800427. Licensed CC0.

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