# Inflammatory Challenge in Human Aggression

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2024 · $635,637

## Abstract

Project Summary: While elevations of circulating pro-inflammatory modulators correlate directly with variables
of aggression, and direct application of cytokines to specific cortico-limbic regions in animals elicit aggressive
responding, no studies have tested the hypothesis that acute increases in pro-inflammatory modulators can/will
increase aggressive behavior in humans. We aim to demonstrate a causal relationship between pro-
inflammatory cytokines and aggression in human subjects by showing that an acute pro-inflammatory state, via
endotoxin challenge, will increase aggressive responding, anger ratings, and hostile social cognition, to a greater
degree in “aggressive” (n = 45), compared with “non-aggressive” (n = 45), individuals with mood/anxiety/ stress-
related and/or personality disorders. The proposed study is a double-blind comparison of endotoxin/placebo
challenge in the same individuals (within-subject) as a function of aggression status. Aggressive individuals will
have high lifetime aggression (> 12 on Life History of Aggression: LHA) and be positive for an average of two
anger attacks per week and/or three anger attacks per year that include physical assault of another person
and/or or non-trivial destruction of property. “Non-Aggressive” individuals will be similar diagnostically but will
have low lifetime aggression. “Aggressive responding” will be assessed using the Taylor Aggression Paradigm
(TAP), “Anger” will be assessed by self-reported assessments (POMS), and “Hostile Social Cognition” will be
assessed by the Video-SEIP (V-SEIP) paradigm. The primary plasma pro-inflammatory outcome measures will
be a composite of CRP, IL-6, IL-8, and TNF-α (as in our previous studies). MRI scans will including task-based
scans involving “explicit” and “ambiguous” social threat. We hypothesize that aggressive responding, anger
ratings, and hostile social cognition (Primary Outcomes) and Composite Plasma Pro-Inflammatory Marker levels
(Secondary Outcome), will be greater after endotoxin, compared with placebo, and will be greater in “aggressive”
than “non-aggressive” study participants. We also hypothesize that these variables will correlate with
dimensional measures of aggression. In addition, we hypothesize that amygdala responses to explicit social
threat (anger faces) will be enhanced (greater BOLD fMRI signal response) after Endotoxin, and that cortico-
limbic responses to ambiguous social threat (V-SEIP) will be reduced (i.e., lesser BOLD fMRI signal response)
in all study participants but reduced to a greater extent in “aggressive”, compared with “non-aggressive”, study
participants. Finally, we hypothesize that the pro-inflammatory effects of the endotoxin challenge will result in
reduced connectivity between the functional edges supporting higher aggressive behavior and that endotoxin
challenge will facilitate stronger connections among nodes associated with low aggressive behavior. If
supported, this study will provide a strong rat...

## Key facts

- **NIH application ID:** 10883049
- **Project number:** 1R01MH133925-01A1
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** EMIL Frank COCCARO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $635,637
- **Award type:** 1
- **Project period:** 2024-07-11 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10883049

## Citation

> US National Institutes of Health, RePORTER application 10883049, Inflammatory Challenge in Human Aggression (1R01MH133925-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10883049. Licensed CC0.

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