# Transdiagnostic and Disorder-Specific Effects of Immune and Metabolic Factors on Motivational Deficits Across Mood and Psychotic Disorders

> **NIH NIH R21** · EMORY UNIVERSITY · 2020 · $429,000

## Abstract

PROJECT SUMMARY
Symptoms related to low motivation are common to many psychiatric disorders, particularly mood and
schizophrenia spectrum disorders. These motivational deficits have been associated with elevated
inflammatory markers across these disorders. Significant clinical and preclinical data indicate that effects of
inflammatory mediators on dopamine (DA) in the ventral striatum may mediate the association between
inflammation and decreased motivated behavior. In a related fashion, increased inflammation is associated
with a shift in immunometabolism away from the more energy efficient oxidative phosphorylation to the
relatively inefficient aerobic glycolysis. This shift in metabolism significantly depletes available energy
resources that may be communicated to the brain through effects of inflammatory mediators on striatal DA in
order to constrain motivation and conserve energy resources during periods of heightened immune activation.
To date, however, it remains unknown whether these striatal DA-immune interactions represent a
transdiagnostic mechanism for motivational deficits across different disorders. The focus of this proposal is to
determine whether elevations in inflammation and related immunometabolic changes represent a common
mechanism for impairments in motivation across disorders of psychosis and mood. Given that recruitment of a
well-powered transdiagnostic sample would not be possible under an R21 mechanism, this proposal is
uniquely poised to leverage data collected by R01MH066031 (PI: Barch) at Washington University.
R01MH066031 is recruiting a transdiagnostic sample to assess behavioral and neuroimaging measures of
motivation, including effort-based decision-making (EBDM) paradigms and ecological momentary assessment
(EMA). The focus of the current proposal is to expand this project through the analysis of protein and genetic
markers of immune activity and immunometabolism from this sample. Specifically, using blood samples
collected from patients with unipolar depression, bipolar depression, schizophrenia, and schizoaffective
disorder (n = 50 per group) as well as 75 healthy controls, elevations in inflammatory markers and their
relationship to EBDM and EMA measures of motivation will be compared across groups (Aim 1). In Aim 2, we
will assess different levels of gene expression within pathways of inflammation and immunometabolism and
will relate changes to specific immune cell subsets using transcript-of-origin analyses. In particular, we will test
whether enriched expression of genes in inflammatory pathways (e.g. NF-kB) and pathways related to
glycolysis (e.g., insulin, MTOR, AKT, PI3K) localized within specific immune cells (e.g. monocytes) predicts
reduced effort during EBDM and EMA measures. These data will help determine the extent to which potential
immunotherapies, including anti-inflammatories and/or regulators of immunometabolism can confer disorder-
specific or transdiagnostic benefits to patients with mood o...

## Key facts

- **NIH application ID:** 9979349
- **Project number:** 1R21MH119622-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Michael Tilghman Treadway
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $429,000
- **Award type:** 1
- **Project period:** 2020-04-15 → 2024-04-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979349

## Citation

> US National Institutes of Health, RePORTER application 9979349, Transdiagnostic and Disorder-Specific Effects of Immune and Metabolic Factors on Motivational Deficits Across Mood and Psychotic Disorders (1R21MH119622-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9979349. Licensed CC0.

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