# Impact of Inflammation on Reward Circuits, Motivational Deficits and Negative Symptoms in Schizophrenia

> **NIH NIH K23** · EMORY UNIVERSITY · 2021 · $191,484

## Abstract

Project Summary/Abstract
The proposed research and training plan is designed to promote my development as an independent
investigator in the field of brain-immune interactions as they relate to negative symptoms in schizophrenia.
Negative symptoms, including motivational deficits, are some of the most debilitating aspects of the disorder,
being both difficult to treat and representing one of the most significant barriers to functional recovery.
Regarding potential mechanisms of these deficits, individuals with schizophrenia reliably show decreased
activation of the ventral striatum in reward-based neuroimaging tasks. One pathophysiologic pathway that may
contribute to alterations in reward circuitry in schizophrenia is inflammation. Previous work has demonstrated
that inflammatory stimuli decrease neural activity in the ventral striatum and decrease connectivity in reward-
relevant neural circuitry. In addition, my published work and that of others has found that patients with
schizophrenia reliably exhibit elevated concentrations of inflammatory markers, and my preliminary data
indicate that inflammatory cytokines of monocytic origin, including tumor necrosis factor (TNF), are related to
negative symptoms including decreased motivation and decreased functional connectivity in reward circuitry in
these patients. Based on these findings, I hypothesize that increased inflammation in schizophrenia contributes
to negative symptoms by disrupting neural activity in reward circuits leading to motivational deficits. To test this
hypothesis, I propose the following Specific Aims: (1) To determine the association of inflammation with
objective and clinical measures of motivation and negative symptoms, such as the Effort Expenditure for
Reward Task, the Intrinsic Motivation Inventory, the Snaith Hamilton Pleasure Scale, and the Brief Negative
Symptom Scale. (2) To determine the association of inflammation with reward circuitry in patients with
schizophrenia using both task-based and resting state functional magnetic resonance imaging. (3) To explore
whether the TNF antagonist, infliximab, will increase connectivity in reward circuitry leading to improvements in
motivational deficits and negative symptoms. This work will inform future studies of novel therapeutic strategies
to treat negative symptoms in patients with schizophrenia. As part of this proposal, I will also train in clinical
research methods, neuroimaging techniques and analysis, immunology, assessments of motivation and
negative symptoms in schizophrenia, and the ethical conduct of research. My development plan combines
formal didactics, workshops, and hands-on training in neuroimaging, immunology, and schizophrenia, in
addition to the proposed research. I have also assembled a team of recognized leaders in brain-immune
interactions, schizophrenia and neuroimaging to provide mentorship during the award period. A K23 award is
critical to my career development because it provides the needed protec...

## Key facts

- **NIH application ID:** 10208667
- **Project number:** 5K23MH114037-04
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** David Ryan Goldsmith
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $191,484
- **Award type:** 5
- **Project period:** 2018-07-02 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10208667

## Citation

> US National Institutes of Health, RePORTER application 10208667, Impact of Inflammation on Reward Circuits, Motivational Deficits and Negative Symptoms in Schizophrenia (5K23MH114037-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10208667. Licensed CC0.

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