Small Protein May Play Big Role in Controlling Aggression
Abstract
A small protein called neuropeptide Y, which can be found in the hypothalamus and some other brain regions, appears to play a key role in aggressive behavior.
An antagonist of neuropeptide Y might be able to temper aggression in some individuals. While it is not available now, other treatments are known to be effective in diminishing aggression.
Animal research has pointed to the validity of this hypothesis, and now a clinical study in humans does so as well. The new study identified a strong link between neuropeptide Y and anger and aggression in human subjects, especially those with personality disorders.
The study was led by Emil Coccaro, M.D., chair of psychiatry at the University of Chicago and an expert on intermittent explosive disorder. The results were published online September 17 in Biological Psychiatry.
Coccaro and his colleagues recruited subjects for their study through public-service announcements seeking individuals who considered themselves to have difficulty managing their aggressive behaviors, as well as nonaggressive individuals who were willing to participate in a study of personality traits. They ended up with 20 mentally healthy subjects and 40 subjects who met DSM-IV criteria for a specific personality disorder or for a personality disorder not otherwise specified.
Of the 40 personality disorder subjects, most had a lifetime history of at least one Axis I disorder, and half currently had at least one such disorder. Intermittent explosive disorder (IED) was among the most prominent of the disorders, with 11 of these 40 subjects currently having IED and 13 having a history of the disorder.
The researchers evaluated all of the subjects for aggression, using scales such as the Buss-Durkee Hostility Inventory and the Life History of Aggression assessment. They also performed a lumbar puncture on all of the subjects to obtain cerebrospinal fluid samples. They used the samples to measure the levels of neuropeptide Y present in each subject. Finally they assessed whether there was a relationship between impulsive aggression and levels of neuropeptide Y.
Such an association did exist. They found a direct correlation between impulsive aggression levels and neuropeptide Y levels, particularly in subjects with a personality disorder. In addition, neuropeptide Y levels in personality disorder subjects who also had IED were considerably higher than those in personality disorder subjects who did not have IED.
The findings suggest that an antagonist of neuropeptide Y might be able to temper aggression in some individuals. “However, there are no neuropeptide Y antagonists on the market, and I’m not sure if there are any in development right now,” Coccaro told Psychiatric News.
Meanwhile, at least some people with an aggression problem can be helped by cognitive-behavioral therapy, antidepressants, anticonvulsants, antianxiety agents, or mood regulators, Coccaro and colleagues pointed out in their report.
The research was funded by the National Institute of Mental Health and the Swedish Medical Research Council. 
An abstract of “Cerebrospinal Fluid Neuropeptide Y-like Immunoreactivity Correlates With Impulsive Aggression in Human Subjects” is posted at www.biologicalpsychiatryjournal.com/article/S0006-3223(12)00684-1/abstract.
