# Examining the Effects of Estradiol on Neural and Molecular Response to Rewards in Perimenopausal-Onset Anhedonia and Psychosis

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $771,097

## Abstract

Project Summary
Affective disorders are highly prevalent in women and associated with significant morbidity and
mortality, particularly during times of reproductive transition, including the transition to
menopause. Unraveling the pathophysiology of affective disorders is challenging because
depressive syndromes are heterogeneous and have diverse etiologies. Thus, studies aimed at
identifying biomarkers to improve the prediction of susceptibility and illness course as well as
treatment response in affective disorders have yielded inconsistent results. We propose to
address this challenge by studying symptoms that initially present during the menopause
transition and thus have a common endocrine trigger. We believe that studying a relatively
homogeneous group of participants with similar biological mechanisms of symptom onset will
increase the likelihood of elucidating the pathogenesis of perimenopausal-onset symptoms. This
proposal will use simultaneous positron emission tomography and functional magnetic
resonance imaging (PET-MR) to examine relations between reward-related striatal activation
measured by fMRI and tonic and phasic striatal DA activity measured by [11C]raclopride PET in
a transdiagnostic sample of women with varying severities of perimenopausal-onset (PO)
anhedonia and psychosis. Specific Aim 1 will examine associations between PO anhedonia and
psychosis symptom severity and reward-related striatal activation measured by fMRI and tonic
and phasic striatal DA activity measured by [11C]raclopride PET. Specific Aim 2 will examine
relations between anhedonia reductions due to estradiol administration, relative to placebo, and
changes in PET-MR metrics related to reward processing. Specific Aim 3 will examine relations
between PO psychosis reductions due to estradiol, relative to placebo, and changes in PET-MR
metrics related to reward processing. Our central hypotheses are that the mesolimbic dopamine
system is impaired during reward processing in PO anhedonia and psychosis, that the effects of
estradiol administration will be associated with normalization of neural responses to rewards
measured by fMRI and striatal dopamine functioning measured by PET, and that the degree of
change in striatal functioning measured by fMRI and PET will be associated with the magnitude
of change in PO anhedonia and psychosis symptom severity. The results of this project will
increase our understanding of anhedonia and psychosis vulnerability during the menopause
transition and have the potential to deliver validated molecular imaging targets to use in future
mechanistic clinical trials of novel treatments for perimenopausal-onset psychiatric disorders.

## Key facts

- **NIH application ID:** 10348271
- **Project number:** 1R01MH128238-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** GABRIEL S DICHTER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $771,097
- **Award type:** 1
- **Project period:** 2022-01-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10348271

## Citation

> US National Institutes of Health, RePORTER application 10348271, Examining the Effects of Estradiol on Neural and Molecular Response to Rewards in Perimenopausal-Onset Anhedonia and Psychosis (1R01MH128238-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10348271. Licensed CC0.

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