Bridging the Brain and Behavior in Psychiatric Research

Habits are behaviors that, once established, run on autopilot and are notoriously difficult to break. Christopher Pittenger, MD, PhD, became interested in how we establish habits while he was a graduate student. While conducting his PhD research in the lab of Nobel laureate Eric Kandel–whose work uncovered how neurons rewire as we learn–Pittenger began to wonder, if neuronal rewiring could underlie learning, what happens in the brain circuitry that underlies habits?

After graduate and medical school, Pittenger came to Yale School of Medicine (YSM) for his psychiatry residency. He continued his research, exploring habit learning in obsessive-compulsive disorder (OCD) through cellular and molecular studies in animal models.

“I continued my basic science research, but I also took on clinical research, and that led me in a direction that really wasn't expected or planned,” says Pittenger, Elizabeth Mears and House Jameson Professor of Psychiatry at YSM. “I thought, if the basic phenomena that I'm studying in these animal systems are relevant to OCD, I ought to learn something about OCD.”

During his final year of residency, Pittenger joined the Obsessive Compulsive Disorder Research Clinic at YSM. He now directs it, and his lab models disease pathophysiology and investigates new treatment strategies for obsessive-compulsive disorder, Tourette syndrome, and related conditions.

“There is a lot of serendipity involved in my journey,” he says.

For Pittenger, transitioning from basic neuroscience to clinical research, a move driven by curiosity, required institutional support and funding. “I was a good scientist and well-trained as a clinician, but clinical research was a different beast," Pittenger says. "It required different techniques, regulatory structures, and statistics."

The Yale Center for Clinical Investigation (YCCI) at YSM, however, provided Pittenger with guidance. The mission of YCCI is to accelerate clinical and translational research by providing infrastructure, funding, and mentorship to investigators across Yale. For a researcher like Pittenger who was pivoting into new territory, this support proved transformative.

In 2009, YCCI provided Pittenger with critical early support through the YCCI Scholar Award, which allowed him to build momentum in clinical science while maintaining his basic research. "Without that support, I probably would have just continued doing lab work," he says. Later, in 2011, the YCCI Pilot Program, which aims to fund scientifically meritorious projects, enabled him to launch an entirely new research direction studying Tourette syndrome.

The Pittenger lab approaches their work from multiple angles, combining insights from molecular biology, brain circuitry, psychology, and clinical treatment.

At the molecular level, his team is studying genetic mutations that cause conditions like Tourette syndrome, tracing how mutations in a single gene can disrupt brain development. At the cellular level, the research team investigates how early-life stress rewires brain circuits differently in males and females. And on the treatment side, Pittenger’s team has completed several clinical trials, including the first placebo-controlled study of psilocybin as a therapeutic for OCD.

This multi-pronged approach is essential, says Pittenger, because unlike kidney disease or pneumonia, psychiatric disorders aren't well-defined entities.

"It's not just a cellular problem. It's not just a neurotransmitter problem. It's not just a neural circuit problem. It's not just a psychological problem,” Pittenger says. “We need to integrate across all of these levels, and that's really hard." His lab’s success in doing that, he says, is due to the people he’s brought in.

"Our research program has grown to be very broad because I've been fortunate in the trainees who've come to work with me," he says. "They bring new perspectives to the work. We develop new ideas together, and when they succeed, I succeed too."

OCD is the main focus of the lab, and while they work to uncover its drivers, they’ve also become acutely aware of how misunderstood it is. OCD is not what popular media discourse makes it out to be, Pittenger says. “The way OCD is depicted in the media is that it is cute, and not that big of a deal—but nothing could be further from the truth for people who are really suffering from this clinical disorder.”

Like all psychiatric diseases, OCD is extremely complex. In the media, OCD is often centered around excessive cleaning. While around 30% of people with OCD have contamination fears, they aren't preferences for cleanliness, Pittenger says, they're consuming worries about being the source of a plague that might cause harm to them or their family.

“It's on a continuum with having a disturbing thought pop into your head, turned up by a factor of one hundred or a thousand,” Pittenger says. For people who suffer from severe OCD, it can be a life-destroying illness, and there is a growing acceptance of that, thanks to advocacy organizations like the International OCD Foundation, where Pittenger serves in leadership.

Beyond his own career, Pittenger now directs the research track within Yale's psychiatry residency and mentors dozens of junior clinician-scientists. "Seeing how YCCI is doing the same thing for people 10 years junior to me that it did for me early in my career is really great,” he says.