School of Medicine

On the frontiers of psychiatry

Steven J. Mennerick, PhD, prepares to use a collection of technology — including a microscope and amplifiers — to measure the tiny electrical impulses between brain cells. The equipment helps him assess how the electrical conversations of neurons are influenced by therapeutic drugs. (Photo: Matt Miller)

Physician-scientists aim to reduce the impact of mental illness on society

From the WashU Outlook Magazine

Up to one-third of the 16 million Americans with clinical depression don’t get relief from antidepressant drugs. As a result, they endure continuing sadness, problems with sleep, and often, difficulty concentrating, so that reading a book or functioning at work is problematic. Some even contemplate and attempt suicide. And the impact extends to family and friends…

…At Washington University’s Taylor Family Institute for Innovative Psychiatric Research, investigators are looking for new solutions. Their ultimate goal: Reduce suffering and diminish the impact of psychiatric illnesses on society…

…Private funding = fast progress

The institute was created in 2012 through private funding from the university’s Leading Together campaign. Its founding mission: to provide flexible funding to foster and streamline efforts in basic research, clinical research and drug development as scientists work across disciplines to uncover new ways to treat psychiatric illness. Members of the institute collaborate among several departments, including psychiatry, anesthesiology, developmental biology, radiology and neurology.

“The institute really was founded on the premise that we need flexible funding to support pipelines of research development, rather than focusing on individual projects in specific departments,” said Steven J. Mennerick, PhD, a professor of psychiatry and of neuroscience and the institute’s scientific director. “Government grants tend to be very specific, so to take a project to the next step, you need another grant, and then another. But with flexible funding through the institute, we can partner — quickly — with people who have expertise in other areas of science or drug development, and we can make progress faster than is possible with traditional grants.”…

…A new treatment target

Although the institute only has been around for a handful of years, some of its members have been studying natural and synthetic neurosteroids for several decades. That work began in 1993, when Douglas F. Covey, PhD, then a professor of molecular biology and pharmacology, and Charles F. Zorumski, MD, then an associate professor of psychiatry, were part of a Program Project Grant from the National Institutes of Health (NIH) to study neurosteroids for their anesthetic effects. Their process: Covey’s lab synthesized neurosteroid molecules, and Zorumski tested them in brain cells….

“In those early days, we mostly were trying to learn about whether these molecules had anesthetic effects, and if so, how they might work,” said Covey, a professor of developmental biology, of anesthesiology and of psychiatry. They discovered that neurosteroids weren’t working through serotonin receptors the way SSRIs did. Instead, many were influencing gamma-aminobutyric acid (GABA) receptors, the same neuronal receptors affected by anesthetics.

Fast-forward about 20 years. By the spring of 2012, Covey had made hundreds of synthetic neurosteroids, some of which seemed to have the potential to alleviate symptoms of depression. And Zorumski, now the Samuel B. Guze Professor, head of the Department of Psychiatry and professor of neuroscience, believed that after years of making and testing neurosteroids, they had a good handle on how the molecules interacted with two types of receptors in the brain: GABA receptors and excitatory glutamate receptors. They could, he thought, be on the verge of identifying neurosteroids to alleviate depression and other psychiatric disorders.

“Some of these neuroactive steroids were potent anesthetics, but we believed others were going to prove to be useful for treating several psychiatric disorders,” Covey said.

  Read more in the Outlook Magazine.