BBRF Celebrates 30-Year Anniversary While Honoring Innovative Researchers

While some breakthroughs arise from completely new discoveries, others occur when existing knowledge is viewed from a different angle.

So said John Davis, M.D., the Gilman Professor of Psychiatry and Research at the University of Illinois at Chicago, during a lecture at the 30th annual Brain & Behavior Research Foundation (BBRF) Research Symposium. Davis is the recipient of BBRF’s 2017 Lieber Prize for Outstanding Achievement in Schizophrenia Research.

During the lecture, Davis recalled that his asking new questions about existing data in the 1960s eventually changed the way that psychiatrists viewed maintenance therapy for individuals with mental illness.

At that time, most psychiatrists viewed psychotropic drugs primarily as short-term fixes to stabilize patients with severe agitation or depression. Davis knew of some studies that suggested otherwise, showing that the longer patients used antipsychotics and antidepressants, the lower their risk of relapse. He combed through the literature and wrote a study that combined the research data and in 1965 published what he said was the first-ever meta-analysis in psychiatry. That analysis led to a greater appreciation of the benefits of prescribing psychiatric medications for long-term maintenance therapy. Today, clinical trials assessing maintenance treatment and relapse risk are standard requirements for companies seeking Food and Drug Administration approval for a psychotropic drug, he said.

The idea of taking a new look at existing knowledge was a theme throughout the day-long symposium, which the BBRF holds every year to highlight recent advances and emerging frontiers in psychiatric research.

Chad David Kraus

During her lecture at the symposium, Deanna Kelly, Pharm.D., B.C.P.P., the recipient of the Maltz Prize for Innovative and Promising Schizophrenia Research, described her research on the connection between wheat and schizophrenia risk. Epidemiological studies have hinted at this association for decades; cohorts of children born during lean wheat years—such as occurred in Europe during World War II—tend to have lower rates of schizophrenia as they age. Subsequent studies by Kelly and her colleagues suggest that in some people with schizophrenia, gliadin proteins, a component of gluten, are elevated and found to be associated with high peripheral and central inflammation, representing a potential subgroup who may benefit from targeted treatments. About 30 percent of people with schizophrenia produce antibodies in response to gliadins, compared with 10 percent of the general population.

Kelly, a professor of psychiatry at the University of Maryland School of Medicine, highlighted some of her recent clinical studies looking at a group of schizophrenia patients who have high levels of gluten antibodies and other signs of elevated inflammation. Studies in Kelly’s lab found patients who switched to a gluten-free diet supplemented with rice flour shakes reported fewer negative and cognitive symptoms. Similar improvements were not seen in patients who were on the same diet but consumed gluten-containing wheat flour shakes instead of rice flour shakes. She has a larger, confirmatory clinical trial under way, and she and her collaborators are looking at underlying mechanisms tied to findings in this schizophrenia subgroup related to inflammation and gut permeability.

A scientific observation even older than the schizophrenia-gluten connection is the role of glial cells in repairing nerve damage. “Glial cells are the first responders to stress in the brain—that’s been known for 100 years,” said Anna Molofsky, M.D., Ph.D., an assistant professor of psychiatry at the University of California, San Francisco School of Medicine.

Molofsky’s lab is using advanced tools such as genomics and brain imaging to better understand glia, particularly their role as molecular garden shears that prune damaged neurons.

In addition to removing damaged neurons, glial cells must prune functioning neurons during the normal course of human development. As Molofsky explained to the audience, while artistic renditions of neural connections display a lot of “open space,” the brain is quite crowded. “If you want to make a new connection, you have to take something away,” she said.

Glia and their companion astrocytes normally work together to prune neural connections in a tightly regulated manner, she said, but if something goes wrong, that can lead to schizophrenia or neurodegenerative diseases. Molofsky hopes to find clues about what triggers glia to prune improperly; this may help with the development of strategies that can prevent or delay mental illnesses such as schizophrenia.

Research such as that presented at the symposium showcase why “mental health is the most fascinating and demanding area of medicine,” said Hebert Pardes, M.D., president of the BBRF Scientific Council and executive vice chair of the Board of Trustees at New York-Presbyterian Hospital, in his keynote address.

Pardes, who is a past APA president and former director of the National Institute of Mental Health, said he is optimistic that psychiatry is poised for tremendous advances.

“Could I promise a cure for this illness or that illness tomorrow? No! But I can promise you that we now have an army of people who are going to push the understanding of mental illness in as aggressive a way as possible. There have been results—there will be more results,” he said.

Pardes expressed his appreciation to the donors of BBRF, who have contributed over $380 million for research over the past 30 years, establishing BBRF as the largest private funder of mental health research grants in the world.

He then reflected on BBRF’s beginnings. In 1987, the Board of the BBRF (then known as the National Alliance for Research on Schizophrenia and Depression) discussed whether the foundation should spend its funds out of concern about being able to raise more.

“Who would have thought 30 years ago that our discussion of whether to set aside $50,000 for grants would turn into a multimillion dollar enterprise?” ■