James Potash on the Path from Gene to Patient Care in Psychiatry at Johns Hopkins
Institutional Feature, February 2011
Page: < 1 | 2 >
Do teamwork and collaboration entail significant involvement of your researchers with groups in other departments within your institution?
There have been deliberate efforts to create a large number of linkages across departments, particularly between our psychiatry department and the Institute of Genetic Medicine at Hopkins. So we have collaborations with most of the major genetics and epigenetics researchers. And yes, our chairman Dr. DePaulo has been very interested in promoting that collaborative process to bring the best of what Hopkins has in those basic science disciplines to bear on psychiatric problems.
Have there been any particular technological advances that have been important in the evolution of psychiatric research at JHU?
"...how do we get from the genes to making a difference for patients?"
Certainly as a field, psychiatric genetics is at a very, very exciting point. People were working in this field for 20 years—from 1987, say, to 2007—and they made almost no meaningful progress. One thing that did happen, which turned out to be very, very valuable, is that very large samples were amassed. Eventually those samples could be assayed with these incredibly powerful new technologies—genome-wide SNP genotyping assays and genome-wide copy number assays—and those two have turned up some really very, very strong candidate genes now for these major mental illnesses just in the last three years.
Your choice of years for the period in which psychiatric genetics was stalled was very precise—1987 and 2007. What happened in those particular years that made you single them out?
1987 saw the first reports of genetic linkage studies in major psychiatric illnesses. More and more linkage studies were done over the next 20 years, and those linkage studies really did not yield anything anybody felt confident about. But as of three years ago, 2007, that all changed. The first genome-wide association studies were reported in psychiatric illness and about that time the first copy number variation studies were reported. And, in both of those areas, there were some robust, exciting results.
What capabilities do you see as key to the future of psychiatric research at JHU?
I think the ability to continue doing genome-wide studies, at higher and higher levels of resolution, is going to be key. The ability to do very high-resolution genome-wide methylation studies is one of the really exciting capabilities that we have at Hopkins that is going to drive the field of biological psychiatry in coming years. Next-generation DNA sequencing methods—more and more powerful and lower cost—are also going to drive the field.
It's a very, very exciting time because it's still the case that little is understood about the biological underpinning of these major diseases. It feels as if we're on the verge of being able to break it open for the first time ever. While we have treatments for the major mental illnesses, and those treatments are fairly good—they help the majority of people get better—there's still a very large minority of patients who don't benefit.
For example, 30% of people with depression are so-called treatment resistant. They are chronically depressed and the drugs don't help. So there's a big chunk of people who are not getting help. Obviously we have to do better, and the key to doing better, to developing rational treatments that help these patients, too, is to better understand the pathophysiology and etiology of the diseases, and I think we're on the verge of really doing that.
What were the greatest challenges for your institution in performing and presenting its work?
One of the reasons why biological research in psychiatry is so difficult—and this is a fundamental problem in the field—is that unlike, say, in cancer, where we can cut out somebody's prostate, take a biopsy, and put it under the microscope, we can't access the key tissue in psychiatry. We can't get people's living brain tissue, and therefore we have to rely on alternative approaches that are not entirely satisfying.
We can get post-mortem brain tissue, for example, but the numbers aren't so big and the potential for artifacts are big. We can look at the brains of mice and rats, but it's hard to be certain that whatever behaviors we see in those animals actually represents the behavior we see in our patients—is what we're seeing really like the human illness? And this is an obvious problem because the disease involves the brain, and the human brain is so unique. Animal models can be challenging in any disorder, but here it's a particular problem.
So the challenge is getting inside this black box, figuring out ways to see inside. In this sense, brain imaging is getting better and better. MRIs, for instance, are getting higher and higher in resolution. In fact, we're just initiating a study that uses the latest 7 Tesla MRI to see in more detail than ever what's going on inside the living brain.
James B. Potash, M.D., M.P.H.
Arlene and Robert Kogod Associate Professor
Department of Psychiatry and Behavioral Sciences
The Johns Hopkins University School of Medicine
Baltimore, MD, USA
Page: < 1 | 2 >
JHU'S MOST CURRENT MOST-CITED PAPER IN ESSENTIAL SCIENCE INDICATORS:
KEYWORDS: MOOD DISORDERS, CLINICAL CARE, GENETICS, NEUROSCIENCE, NEUROPHARMACOLOGY, CLINICAL TRIALS, EDUCATION, BRAIN IMAGING, BIPOLAR DISEASE, ALZHEIMER'S, DEPRESSION, CLINICAL EPIDEMIOLOGY, CACHE STUDY, OBSESSIVE-COMPULSIVE DISORDER, EPIGENETICS, COLLABORATIONS, PSYCHIATRIC GENETICS, GENOME-WIDE ASSAYS, COPY NUMBER VARIATION, BIOLOGICAL PSYCHIATRY.