# Neuroinflammatory Mechanisms of Anhedonia in Major Depression

> **NIH NIH K23** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $162,455

## Abstract

PROJECT SUMMARY
This proposal seeks to investigate striatal inflammation as a key predictor of brain reward circuitry dysfunction
and anhedonia in patients with major depressive disorder (MDD) using simultaneous positron emission
tomography (PET) and functional magnetic resonance imaging (fMRI). Anhedonia is a core feature of MDD
and inflammation is hypothesized to be an important pathophysiologic factor in the etiology of anhedonia.
Experimentally-induced inflammation and higher peripheral cytokine levels predict alterations in brain reward
circuitry functioning, including decreased striatal response to reward and impaired dopaminergic functioning.
However, no human imaging study to date has provided direct evidence that neuroinflammation is related to
neural response to rewards and clinical symptoms of anhedonia. This represents a critical gap in
understanding how inflammatory processes in the brain contribute to deficits in brain reward function and
increased risk for anhedonia in MDD. Simultaneous PET-fMRI is suited to bridge this gap by directly measuring
both neuroinflammation and functional neural responses to rewards. We propose to collect simultaneous PET-
fMRI from unmedicated MDD patients with clinically significant anhedonia and matched healthy controls using
the radioligand [18F]PBR111 to assess 18-kDa translocator protein (TSPO) expression, an index of
neuroinflammation. We will evaluate group differences in striatal inflammation and frontostriatal activation to
anticipation and receipt of rewards (Aim 1), correlations between PET-derived measures of striatal inflammation
and fMRI-derived measures of frontostriatal activation to rewards in the MDD group (Aim 2), and correlations
between PET-derived measures of striatal inflammation and anhedonia severity in the MDD group (Aim 3).
Mentorship: Experts from UNC-Chapel Hill, Harvard, and Northwestern will mentor the candidate: Gabriel
Dichter, Ph.D., will guide overall professional development and provide training in functional neuroimaging and
the neurobiology of anhedonia; David Lalush, Ph.D., will provide conceptual and methodological training in
simultaneous PET-fMRI imaging; Susan Girdler, Ph.D., will mentor in broader career development and provides
expertise in mood disorders; Young Truong, Ph.D. contributes expertise in neuroimaging statistics; Jacob
Hooker, Ph.D. and Diego Pizzagalli, Ph.D., provide practical PET-fMRI training opportunities with diverse
designs and clinical samples; Gregory Miller, Ph.D., Robin Nusslock, Ph.D., and Keely Muscatell, Ph.D.,
contribute expertise and training in psychoneuroimmunology. Career Development: This award provides the
necessary training to become an expert in the neurobiology of anhedonia and multi-modal imaging and the
experience to succeed as an independent research scientist. Career Goals: This is the first step in a program
of research that seeks to use simultaneous PET-fMRI to investigate neuroinflammatory mechanisms of
anhedonia acr...

## Key facts

- **NIH application ID:** 10216640
- **Project number:** 5K23MH113733-04
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** ERIN WALSH
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $162,455
- **Award type:** 5
- **Project period:** 2018-08-18 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10216640

## Citation

> US National Institutes of Health, RePORTER application 10216640, Neuroinflammatory Mechanisms of Anhedonia in Major Depression (5K23MH113733-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10216640. Licensed CC0.

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