A leap of faith for adolescent behavioral health

As a post-doctoral researcher examining adolescent drug addiction at Harvard’s McLean Hospital between 2006 and 2008, Heather Brenhouse took what her mentor called a “Friday afternoon flyer,” or a leap of faith. The move set the foundation for the research program she is now building as a newly appointed assistant professor of psychology in the College of Science at Northeastern University.

A decade earlier, Brenhouse was working at a biotech firm exploring the inflammatory nature of Huntington’s disease, with a particular interest in a type of anti-inflammatory drug akin to Ibuprofen, called a COX-2 inhibitor. She began wondering how many other diseases this drug type might help treat. “It had always been a bee in my bonnet.”

By the time she reached McLean, Brenhouse had switched gears and began looking at the impact of early-life stress on adolescent behavioral disorders. “I’m interested in learning how early experiences can derail normal development of the brain,” she said. “And how that makes the brain around adolescence vulnerable to disorders like addiction, depression and schizophrenia.”

Researchers had already demonstrated that these diseases cause both inflammatory and behavioral symptoms. Brenhouse wanted to figure out how, why and when the connection between the nervous and immune systems is made. “The more I looked into it, the more I realized, well, let’s try a COX-2 inhibitor.”

In 2011, Brenhouse administered COX-2 inhibitors to rat pups that had been isolated from their mother for hours a day. She then let them grow up under normal conditions and looked at their brains once they reached adolescence. The subset of pups that received the anti-inflammatory seemed to have developed normal brains. On the other hand, those that did not receive the drug were deficient in a type of nerve cell called an interneuron.

Now at Northeastern, Brenhouse plans to examine this phenomenon further. The research is still in the early stages, but she has an idea of what might be going on. “What’s really fascinating about the brain is that different parts of it develop at different times,” she says. She notes that parts of the brain that are important for basic life functions develop earlier than others like the cortex, which plays a role in decision making and begins to develop in adolescence.

According to Brenhouse, adolescent exposure to stress directly affects the developing parts of the brain. “As the brain matures, those areas start to connect to the cortex,” she explained. “If the development of these early structures is derailed, those connections are also dysfunctional.”

Making matters worse is the fact that the immune system is also affected by early life stress and begins to send confused messages to the adolescent brain. Brenhouse implicates neural receptors and immune signals: “We believe they interact, the interesting part is going to be to figure out how.”

Brenhouse, PhD’05, expressed her excitement in returning to Northeastern, a university that she says encourages risk taking. “Sometimes you have to do the safe thing,” she said. “But the big leaps are important, too, and the most fun.”