Searching for Signatures of Anxiety

“We don’t yet have a great sense of what areas of the brain we should stimulate to treat psychiatric disorders.” Lisa Gunaydin, PhD

As a little girl, Dr. Lisa Gunaydin spent long afternoons perched on a filing cabinet in her father’s charmingly cluttered office at Penn State University, where he worked as a theoretical physicist. Wrapped in one of his many musty, elbow-patched sweaters, she flipped through textbooks and dreamt of a life defined by curiosity and learning. While Dr. Gunaydin didn’t choose physics – a subject that she says still baffles her – she did achieve that lifelong goal and now works as a professor and scientist in the UCSF Weill Institute for Neurosciences, where she divides her time between psychiatry and neurodegenerative diseases. With the support of the Weill Innovation Award, Dr. Gunaydin hopes to find cellular and circuit biomarkers for susceptibility to anxiety disorders. This represents an important step in the search for new treatments for these diseases, which currently affect more than 3 million American adults.

How the project will work: “On the molecular side, I’ll collaborate with proteomics and genomics experts to look for specific molecular signatures of anxiety and compulsive behavior. At the same time, I’ll use neural recording techniques to measure differences in circuit activity between the brains of normal mice and mice with traits similar to those seen in humans with severe anxiety or compulsive behavior. It’s the perfect time to do this work because we have amazing new tools that allow us to understand the brain in totally new ways.”

Why this work is crucial: “We don’t yet have a great sense of what areas of the brain we should stimulate to treat psychiatric disorders. By rigorously using these new techniques to systematically go through different brain areas and cell types, we’ll get a much better sense of the neural circuits involved in these behaviors, which might ultimately inform the placement of electrodes in deep brain stimulation. At the same time, the molecular signature work we’re doing might help us find proteins that could make good targets for drugs to treat anxiety and compulsive behavior.”

A new approach: “Traditionally, scientists have stumbled upon psychiatric medications, finding things that worked but not really understanding how or where in the brain they worked. These drugs bathe the entire brain, often causing many side effects because of their lack of specificity. To develop new treatments that target the precise problem, we need this more rational approach to understanding cellular and circuit mechanisms, which we hope will ultimately lead to new therapies.”

What the award means to her: “I’m a new investigator at UCSF, and I’m just beginning to get things off the ground. Support from this award allows me to hire more high-quality people and be ambitious with my experiments, incorporating many different techniques and involving great people in my work.”

What drives her: “I’ve always been fascinated by behavior. In college, I took a seminar that explored the amazing effects different hormones can have on behavior. I learned that just by changing the expression pattern of a single gene in the brain, you can turn a polygamous animal monogamous. That just blew my mind and introduced me to how these tiny changes can have huge effects. It also illuminated this huge knowledge gap: we know the brain is controlling behaviors, and hormones are acting on the brain, but we don’t know what’s happening in the brain to produce those behaviors. I’m hoping to help fill that knowledge gap.”

UCSF Weill Awards

Joseph DeRisi, PhD; Samuel Pleasure, MD, PhD; and Michael Wilson, MD