Feb 14, 2020 9:30 AM

Author: Shaun Ajay


Many psychologists have looked into patterns of violent behavior for years, however only a handful have researched the biological implications. A researcher at University of Utah Health is looking at the causes of violence, or impulse-control, at the biological level. What really happens in our brains during violent outbursts? How and when does violence become compulsive? And are there drugs that potentially ‘cure’ this behavior? 

Marco Bortolato, MD PhD, is an associate professor of pharmacology and toxicology at the College of Pharmacy. His background as a physician doing both clinical and pre-clinical research prompted him to study the problems found in both neurology and psychiatry. “Drug development and therapeutic treatments was very much my natural ambition,” Bortolato says. 

Marco Bortolato portrait
Marco Bortolato, MD PhD

In 2002, he first began studying agression and the therapeutic effects of cannabinoids, a compound present in marijuana. He then shifted his focus to impulse-control disorders such as Tourette syndrome and schizophrenia. ‘Impulsivity’ is defined clinically as the uncontrollable tendency to do something despite having potentially adverse consequences. It is common to many psychiatric issues including antisocial behavior drug addiction, risk-taking behavior in pathological gambling, and some movement disorders such as Tourette syndrome . 

Bortolato started looking into clinical evidence of the interplay between genetic predisposition to impulsivity and exposure to stressful environments and how this can lead to greater risk for psychiatric problems.

His approach is to carry out a three-step process to determine the biology behind violence, and subsequently a treatment that addresses these biological changes. Bortolato first has to identify reliable clinical information, i.e., looking at evidence that for a given disease certain types of predispositions do exist, such as abuse during upbringing at home or use of a certain drug. 

“This sort of study is complicated and can take several years because you have to identify a suitable test model to replicate specific aspects of the human diseases,” Bortolato says. Something that is reproducible, from the genetic predispositions to violence, to the environmental factors, has to be recreated in animal models. By replicating these sequences of patterns that tend to occur in psychiatric patients, he hopes to show how pathological aggression or antisocial behavior are underpinned by biological alterations in the brain. 

Establishing these patterns, he then determines an animal model that is relatively similar in outcomes both in face perspective and neurobiological changes (disfunction in one or multiple given brain regions). The model is then used to make predictions on the pathology, aspects of the disease that we might not know in humans, and molecular pathways that underlie these changes. Currently his studies with mice show that they engage in similar risky and disadvantageous behaviors that mimic the decision-making process of people when they gamble.

“Now that we have a biological tool to actually study this development of violence, we could potentially predict who is at risk and hopefully intervene with treatment at an earlier stage.”

The final goal is to develop drugs and test their effectiveness in a clinical trial.

Bortolato has reached that step with a related project. A clinical trial in Denmark set for the end of this year will test new drugs aimed at reducing the negative effects of stress on tic exacerbation in children with Tourette's syndrome.

To continue making inroads into this field of research, Bortolato has established a consortium with Sheila Crowell, PhD, (Psychology) and Brooks Keeshin, MD, in the department of Pediatrics, called the Utah Program of Research on Violence, Etiology, Neurobiology and Treatment (U-PReVENT).

“Violence is a huge issue in this country, and its estimated impact and damages are in the hundreds of billions but the biological basis of violence remains greatly understudied,” says Bortolato. “If we get to a decent understanding of how vulnerability factors interact and ultimately lead to aggression, we might be able to reduce the problem of those at risk.”  

 

 

Photo credit: Jacqueline Schneider

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