Markers of inflammation in the blood may be linked to aggressive behaviors like intermittent explosive disorder (“road rage”), according to a recent JAMA Psychiatry study.
This may mean simple drugs, from aspirin to Celebrex, may help with aggressive personality problems.
“We thought based on the literature that we would find a relationship between aggression and inflammation,” University of Chicago behavioral neuroscientist Emil Coccaro tells Drug Discovery & Development. That is exactly what the group found. The only surprise says Coccaro, chairman of the Department of Psychiatry and Behavioral Neuroscience: the discovery that it was “aggressive behavior, not aggressive thoughts, that went with the elevation of inflammatory markers.”
Intermittent explosive disorder (IED) is a mental illness involving impulsivity, hostility and recurrent aggressive outbursts. After examining 200 subjects, Coccaro’s group determined that people with the disorder possess hiked levels of two common markers of systemic inflammation in the blood: C-reactive protein (CRP) and interleukin-6 (IL-6).
Coccaro’s is the first controlled study to find a direct link between those inflammatory markers and recurrent, problem-causing aggression in people diagnosed with intermittent explosive disorder—but not in the mentally healthy, or those with other psychiatric disorders.
Coccaro’s team does not yet know which came first—the aggression, or the inflammation. But the team has established a biological link between the two.
People with IED can overreact to stress, often with uncontrollable rage. In the past, IEDs have been called tempers, but science increasingly finds they are serious conditions with biological roots that should be treated.
IED can lead to other mental illnesses, like drug-abuse and depression, and to physical illnesses ranging from stroke to ulcers, diabetes and heart conditions, according to a 2010 Coccaro study.
In 2006, Coccaro and psychiatrists at Harvard Medical School found IED afflicts up to 5% of American adults. The first episode of rage occurs in adolescence: age 13 for males, age 19 for females.
In the recent JAMA report, Coccaro examined blood levels of CRP and IL-6, each of which has been associated with both inflammation, and impulsive aggressive behaviors, in mice, cats and humans.
CRP is generated by the liver in response to infection or injury. It draws the attention of the immune system to necrotic or injured cells. White blood cells emit IL-6 to generate robust immune responses like fever. IL-6 also jacks up production.
Cocarro’s team measured CRP and IL-6 levels in 197 physically healthy volunteer subjects. Sixty-nine had been diagnosed with IED and 61 with psychiatric disorders not involving aggression. The number with no psychiatric disorder: 67.
On average, CRP and IL-6 levels were higher in those with IED. Average CRP levels were twice as high in those with IED as in healthy volunteers. Both markers were unusually elevated in people with the most lengthy histories of aggressive behaviors—if not aggressive thoughts.
Anti-inflammatories like Celebrex or aspirin may help, as current IED treatments bring remission to fewer than 50% of patients. So Coccaro’s group plans to “examine inflammatory levels in the cerebrospinal fluid that bathes the brain to see if these elevations are also in the central nervous system,” he says.
He notes his group then hopes to “treat people for aggression with standard treatments to see if inflammation goes down when aggressive behavior goes down, and treat aggressive people with an anti-inflammatory to see if blocking the effects of inflammation reduces aggression in people.”
The group is currently doing this research in mice.