Explosive Aggression May Be Neurologic

Jim Kling

August 24, 2021

Aggression is an underappreciated mental health issue, and biological mechanisms might help explain more extreme forms like intermittent explosive disorder (IED), which is characterized by episodes of sudden impulses and inappropriate aggression, violence, or even verbal outbursts. IED can lead to road rage, domestic abuse, in addition to throwing objects and engaging in other destructive behaviors.

Despite those consequences, aggression hasn't gained the same level of attention as other psychiatric conditions, according to Emil F. Coccaro, MD, who spoke about the topic at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

"People seem to think that aggressive behavior is bad behavior, and therefore people just need an attitude adjustment. So there's this sort of stigma, and there are no advocacy groups for it. There are no poster children for it. But there's a whole lot of biology and neuroscience behind it," said Coccaro, in an interview. He is a professor and vice chair of research in psychiatry and behavioral health at Ohio State University, Columbus.

IED is also more common than people generally suspect, with an estimated 4% lifetime incidence, according to Coccaro, who spoke at the meeting presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

There is a general view that psychiatric conditions may lead to increased aggression, but there is little evidence of that. "As a general statement, having a psychological [illness] in and of itself does not really increase the risk of being aggressive. What does is being aggressive in general, and substance use disorder. And the thing with [people who have] substance use disorders is that they only get aggressive when they are aggressive to begin with," said Coccaro, noting that the strongest case for the relationship surrounds alcohol abuse.

The DSM-5 criteria for IED include: verbal or physical aggression without destruction, at least twice per week, or three or more episodes of assault or physical destruction within a year. The behavior must be out of proportion to the provocation, cause distress or impairment, and not be accountable by other diagnoses. "If they're blowing up twice a week, for a few months, and usually they're doing it for a long time, then that's different than just blowing up very occasionally. Healthy people, nonaggressive people, maybe they blow up once a year, or even less frequently than that," Coccaro said.

Functional magnetic resonance imaging and other imaging studies consistently show differences associated with aggression.

"The IEDs really do distinguish themselves from the psychiatric controls. They also have other stuff going on with them; they have a hostile attribution. And they're kind of irritable at baseline. They're not walking around irritable all the time, but the people around them may be walking on eggshells," Coccaro said.

The results from these sorts of studies aren't fully conclusive and can't be used for diagnosis, in part because of a lack of power. "It's hard to do these MRI studies and lots and lots of subjects, because they're kind of expensive," Coccaro said. "We're just not there yet."

Other, less expensive imaging techniques like near-infrared spectroscopy may improve matters. "That might be something down the road that could lead to something (diagnostic). Right now, most imaging studies are being done to really understand mechanisms," said Coccaro.

Those mechanistic studies suggest that the culprit for IED may be a combination of too much drive from subcortical structures like the amygdala and insufficient inhibitor function in the frontal part of the brain. The frontal cortex may suffer a loss of gray matter, according to Coccaro, and there may be insufficient connectivity, which could weaken signals coming from the frontal areas that might otherwise inhibit lower centers of the brain.

Treatment for IED could be aimed at improving that connectivity and signaling. Ketamine and other anesthetic agents like nitrous oxide may increase connectivity to nerve cells by increasing branching at synaptic dendrites.

Selective serotonin reuptake inhibitors have the potential to treat IED, but their utility is limited because they bind to the presynaptic transporter for serotonin, and more aggressive people have fewer of those transporters. "You only get so much bang for your buck," Coccaro said.

Cognitive-behavioral therapy that focuses on anger management and relaxation shows promise. "CBT does help people deal with what's coming at them. So it's like, ‘oh, I'm getting angry, I better start doing those relaxation (techniques).' It teaches them to rethink things."

Dr Henry Nasrallah

During the Q&A session following the presentation, Henry A. Nasrallah, MD, who moderated the session, pointed out that misattribution can occur, leading an affected individual to misread someone's facial expression and react aggressively, which is a problem also seen in psychosis.

"There are studies showing [that if] you show them a series of faces with different affects, many times paranoid patients read a normal facial expression as threatening. So it may be that it's the same thing with aggression," said Nasrallah, who is a professor of psychiatry, neurology, and neuroscience at the University of Cincinnati.

In the midst of the ongoing COVID-19 pandemic, it's also possible that mask-wearing could improve or worsen such misunderstandings. "There is expression in the eyes that you can see, but you miss a lot," Coccaro said.

For now, the effects of masks remain largely unknown. But that will change. "Sooner or later we will have a bunch of papers coming out about how masks have changed a lot of behaviors," Nasrallah said.

Coccaro has consulted for Avanir, Azevan, and Brackett. Nasrallah has consulted for Acadia, Alkermes, Allergan Janssen, Otsuka, Indivior, IntraCellular, Neurocrine, Sunovion, Teva, and Boehringer-Ingelheim. Nasrallah has been on a speaker's bureau for Acadia, Alkermes, Allergan, Janssen, Otsuka, Indivior, Intracellular, Neurocrine, Noven, Sunovion, and Teva.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.


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