Inflammatory Challenge in Human Aggression.
Ohio State University
Summary
The goal of this clinical trial is to explore the differences in behavioral and cytokine response to a low dose infusion of endotoxin (vs. placebo) in individuals with histories of frequent, problematic, impulsive aggression ("aggressives") compared to similar individuals without this history ("controls"). Endotoxin is a substance that produces a reliable inflammation response in human subjects. The main questions it aims to answer are: * Do aggressive individuals have greater self-rated anger responses to low-dose endotoxin compared with controls? * Do aggressive individuals have greater analog aggressive responses (in the Taylor Aggression Paradigm) to low-dose endotoxin compared with controls? * Do aggressive individuals have greater hostile attributional and negative emotional responses (in the V-SEIP) to low-dose endotoxin compared with controls? * Do aggressive individuals have greater plasma pro-inflammatory responses to low-dose endotoxin compared with controls? * Do aggressive individuals display a greater activation of brain responses to anger-related picture during an MRI scan during low-dose endotoxin compared with controls? Researchers will compare endotoxin to a placebo (a look-alike substance that contains no drug) explore the differences in behavioral and cytokine response to a low dose infusion of endotoxin (vs. placebo) in individuals with histories of frequent, problematic, impulsive aggression ("aggressives") compared to similar individuals without this history ("controls"). Participants will: * Receive a low-dose of endotoxin and placebo on two (2) separate days. The study drugs will be given through a plastic tube inserted in a forearm vein. * Visit the laboratory on at least two (2) separate days to receive the endotoxin and placebo. * Complete rating forms, behavioral testing, and an MRI on each of the two (2) laboratory days.
Description
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. The investigators 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, a…
Eligibility
- Age range
- 21–55 years
- Sex
- All
- Healthy volunteers
- Yes
Inclusion Criteria: "Aggressive Subjects" will have a current DSM-5 diagnosis of Intermittent Explosive Disorder (IED) and have a Life History of Aggression (LHA) \> 12. "Control Subjects" will not have current or past history of IED and will have LHA scores \< 11 ("Control Subjects" may have a past, but not current, history of Major Depression (MD), Generalized Anxiety Disorder (GAD), Panic Disorder (PDx), or Post-Traumatic Stress (PTSD) Disorder. Participant is between 21 and 55 years of age and is able to give informed consent. Participant is physically healthy as confirmed by medical h…
Interventions
- BiologicalEndotoxin (E. coli O:113, Reference Endotoxin)
Dosage of endotoxin is 0.8 ng/Kg body Weight
- OtherSaline (Placebo)
Volume of saline to be the same as volume of endotoxin
Location
- The Ohio State University Medical CenterColumbus, Ohio