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KU scientist pursuing new treatments for impulsive aggression

Mon, 10/14/2013

LAWRENCE — Most of us get a little angry, and perhaps even aggressive, now and then. And in most cases, that’s perfectly OK.

Marco BortolatoBut for individuals with pathological impulsive aggression, getting angry can be an altogether different — and dangerous — experience. Their aggression is characterized by impulsive outbursts of violence and anger. These outbursts are typically disproportionate to whatever triggered them, and in many cases, they’re associated with deficits in self-control, along with defiant or hostile behavior.

“We’re talking about uncontrolled and potentially violent outbursts that can have devastating effects for the aggressive individual and those around them,” said University of Kansas neuroscientist Marco Bortolato. “Unfortunately, science hasn’t yet provided adequate tools to really understand and treat the full spectrum of impulsive-aggressive disorders.”

That’s why Bortolato, an assistant professor of pharmacology and toxicology in the School of Pharmacy, is examining the neurobiological basis of impulsive aggression. His goal is to unlock the condition’s underlying mechanisms and ultimately develop treatments for it.

“Like many behavioral disorders, impulsive aggression is currently diagnosed based on symptoms and qualitative descriptors,” Bortolato said. “But we’re looking for biomarkers —biologically based indicators — or other measurable indices that can help us better identify and treat the entire spectrum of pathological aggression disorders.”

The social impact of pathological aggression is substantial, accounting for 60 percent of the 4.5 million violent crimes committed each year in the United States. It’s also a key factor in suicide among male adolescents. The economic toll is equally significant. According to the World Health Organization, the overall costs of impulsive aggression total $200 billion per year when including costs such as medical expenses, legal services and incarceration. 

“There’s clearly a significant social and economic cost,” Bortolato said, “which is why we need to better understand and treat it.”

Searching for biomarkers
In recent years, researchers have begun making headway in their search for biologically based indicators of aggression.

A large body of research, including past work by Bortolato, has zeroed in on the enzyme monoamine oxidase A (MAO A) as a possible biomarker for aggression. Specifically, Bortolato and others have shown that the combination of MAO A deficiency and extreme stress or abuse at a young age can cause pathological aggression in mice and adult males.

In 2011, Bortolato and his colleagues built on these findings by developing the first animal model of this genetic-environment interaction. In particular, he developed a new transgenic line of mice with very low levels of MAO A and then subjected them to early life stress that simulated child neglect and abuse. As expected, the mice demonstrated increased aggression.

In 2012, Bortolato and his colleagues made a breakthrough discovery when they identified a critical neurological factor in aggression: a brain receptor that malfunctions in overly hostile mice. When the researchers shut down the brain receptor, which also exists in humans, the excess aggression disappeared.

Earlier this year, Bortolato used his models to demonstrate that the combination of low MAO A and early life stress can impact learning and memory. Those findings appear in the July 2013 edition of PNAS, the journal of the Proceedings of the National Academy of Sciences.

And most recently, Bortolato used his mice models to demonstrate that the combination of low MAO A and early life stress can increase perseverative behaviors — the repetitive, seemingly purposeless behaviors we often associate with autism. His study appears in the latest edition of the journal Neuropharmacology.

In total, Bortolato’s recent discoveries are further demonstrating the usefulness of MAO A as a potential indicator of aggression.

“By creating these models, we’re able to better identify and isolate possible biomarkers for severe aggression,” he said. “In doing so, we’re getting closer to better prevention, diagnosis and treatment of this condition.”

Bortolato’s current studies on impulsive aggression are funded by the Eunice Kennedy Shriver National Institute of Child Health, as well as grants from the JR and Inez Jay grant from the Higuchi Bioscience Center and the KU COBRE CMADP Pilot Project. 

For more information on Bortolato and his research, visit http://pharmacy.ku.edu/marco-bortolato.



Wanna Skype? Chancellor gets creative to surprise Truman winner. See it here: http://bit.ly/1awodaa
Rock Chalk! Junior Ashlie Koehn named KU's 18th Truman Scholar
Ashlie Koehn, a University of Kansas junior from Burns studying in Kyrgyzstan, interrupted helping her host family prepare dinner to make a Skype call on Monday evening.

.@KU bschool 's KIP team includes @KU _SADP students in all-ages housing project. http://t.co/c6Ss0FsWLL #KUworks http://t.co/FW0eI69uRi
Wanna Skype? Chancellor gets creative to surprise Truman winner From KU News Service: http://bit.ly/1awodaa Ashlie Koehn, a University of Kansas junior from Burns studying in Kyrgyzstan, interrupted helping her host family prepare dinner to make a Skype call on Monday evening. To her surprise, Chancellor Bernadette Gray-Little was on the other end of the call letting Koehn know she had been named a 2015 Harry S. Truman Scholar. Koehn is the 18th KU student to be named a Truman Scholar and the only 2015 recipient from the state of Kansas. Earlier this month, she was also named a 2015 Udall Scholar. And in spite of a distance of more than 10,800 kilometers and 11 time zones, Koehn’s thrill from hearing the news from the chancellor came through loud and clear. “Ashlie’s experience at KU epitomizes a quality undergraduate experience. She challenged herself in her coursework, exposed herself to different research opportunities, studied abroad in Germany, Switzerland and Kyrgyzstan, and participated in both student government and community service projects,” Gray-Little said. “This is quite a year for Ashlie. Her hard work is a wonderful reflection on her and also a great reflection on the university, and we all congratulate her.” Each new Truman Scholar receives up to $30,000 for graduate study. Scholars also receive priority admission and supplemental financial aid at some premier graduate institutions, leadership training, career and graduate school counseling, and special internship opportunities within the federal government. Koehn, a member of KU’s nationally recognized University Honors Program, is majoring in environmental studies, economics and international studies. Her goal after earning her KU degree is to pursue a master’s degree in economics at either the London School of Economics or the University of Reading, with a focus on the economics of climate change. In 2014, she received KU’s Newman Civic Engagement Award for her work establishing the Coalition against Slavery and Trafficking. Her involvement with the issue was sparked by Hannah Britton, associate professor of political science and women, gender, and sexuality studies, who hosted national conference on contemporary slavery at KU three years ago. “Ashlie and I met several times to think about what KU students could contribute to the issue of slavery and human trafficking, and the result was her founding of KU CAST,” Britton said. “After a year as president, Ashlie successfully handed the organization over to the next student leader. She demonstrated her strong leadership qualities by setting a unique goal and then pursuing it with her sense of passion, engagement and dedication. No matter the country or context, her leadership strength is evident in her coursework, her public service and her work experiences.” The University Honors Program works with a campus committee to select KU’s nominees for the Truman Scholarship and supports them during the application process. Anne Wallen, assistant director of national fellowships and scholarships, noted it was an amazing ruse to pull off the surprise. Originally, the call was set up to be between Wallen and Koehn. “I was totally not prepared to be greeted by Chancellor Gray-Little, but it was an amazing surprise for sure,” Koehn said. “As a first-generation student, it took time to learn the collegiate system, but my parents taught me to be resourceful and independent from a young age and KU and the Kansas Air National Guard have provided me with the opportunities to drive me into the future, both at graduate school and in my career. I plan to use the Truman Scholarship to pursue a career as an environmental economist helping to shape future trade agreements and leverage action on important international environmental issues, particularly concerning climate change.” Koehn also had a surprise of her own for the chancellor — the meal she was helping to prepare was not exactly typical Kansas dinner fare. On the menu with her host family in Kyrgyzstan on Monday was a traditional Kyrgyz meal called Beshbarmak, or “five fingers,” because you eat it with your hands. The dish is made of horse and sheep and was being prepared as a birthday celebration for Koehn’s host mom. Chancellor Gray-Little, as she signed off from Skype, made sure to encourage Koehn to enjoy her Beshbarmak. Koehn is the daughter of Rodney and Carolyn Koehn of Burns. She graduated from Fredric Remington High School in Moundridge. She is an active member of the Kansas Air National Guard and currently on leave while studying abroad in Bishkek, Kyrgyzstan. She is a member of the KU Global Scholars Program and a past member of the Student Senate. In addition to being named a 2015 Truman and Udall scholar, she was named a 2014 Boren Scholar and Gilman Scholar and in 2013 was named the Kansas Air National Guard Airman of the Year.


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