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Original Investigation |

Elevated Plasma Inflammatory Markers in Individuals With Intermittent Explosive Disorder and Correlation With Aggression in Humans

Emil F. Coccaro, MD1; Royce Lee, MD1; Mary Coussons-Read, PhD2
[+] Author Affiliations
1Clinical Neuroscience Research Unit, Department of Psychiatry and Behavioral Neuroscience, Pritzker School of Medicine, University of Chicago, Chicago, Illinois
2Department of Psychology, University of Colorado Colorado Springs, Colorado Springs
JAMA Psychiatry. 2014;71(2):158-165. doi:10.1001/jamapsychiatry.2013.3297.
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Importance  Neurochemical studies in human aggression point to a modulatory role for a variety of central neurotransmitters. Some of these neurotransmitters play an inhibitory role, while others play a facilitatory role modulating aggression. Preclinical studies suggest a facilitatory role for inflammatory markers in aggression. Despite this, to our knowledge, no studies of aggression and inflammatory markers have been reported in psychiatric patients or in individuals with recurrent, problematic, impulsive aggressive behavior.

Objective  To test the hypothesis that plasma inflammatory markers will correlate directly with aggression and will be elevated in individuals with recurrent, problematic, impulsive aggressive behavior.

Design, Setting, and Participants  Case-control study in a clinical research program in impulsive aggressive behavior at an academic medical center. Participants were physically healthy individuals with intermittent explosive disorder (n = 69), nonaggressive individuals with Axis I and/or II disorders (n = 61), and nonaggressive individuals without history of an Axis I or II disorder (n = 67).

Main Outcomes and Measures  Plasma levels of C-reactive protein and interleukin 6 were examined in the context of measures of aggression and impulsivity and as a function of intermittent explosive disorder.

Results  Both plasma C-reactive protein and interleukin 6 levels were significantly higher in participants with intermittent explosive disorder compared with psychiatric or normal controls. In addition, both inflammatory markers were directly correlated with a composite measure of aggression and, more specifically, with measures reflecting history of actual aggressive behavior in all participants.

Conclusions and Relevance  These data suggest a direct relationship between plasma inflammatory processes and aggression in humans. This finding adds to the complex picture of the central neuromodulatory role of aggression in humans.

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Figure 1.
Plasma C-Reactive Protein (CRP) and Log Interleukin 6 (IL-6) Levels as a Function of Participant Status

Plasma CRP levels are measured in milligrams per liter and log IL-6 levels, in picograms per milliliter. IED indicates intermittent explosive disorder.aP<.05 different from healthy controls.bP<.05 different from healthy and psychiatric controls.

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Figure 2.
Life History of Aggression (LHA) Aggression Score With Plasma C-Reactive Protein (CRP) and Log Interleukin 6 (IL-6) Levels in All Participants

A, Plasma CPR levels. B, Plasma log IL-6 levels. IED indicates intermittent explosive disorder.

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