Member Spotlight: Dr. James Potash, University of Iowa

James Potash, MD, MPH
Center of Excellence: University of Iowa
Title: Paul W. Penningroth Professor and Chair of Psychiatry
Member of the NNDC Executive Committee and Board of Directors



  • What brought you into the field of psychiatry?
Well, my father was a psychiatrist and my mother was a lawyer who suffered from depression. Both of those influences had a big impact on me. But I decided to become a doctor while I was in the Peace Corps in the West African country of Senegal. For a while I thought I would go into pediatrics or medicine and practice International Public Health. When I got to my psychiatric rotation in medical school I realized that I enjoyed talking to patients more than I enjoyed doing things to them, and that the brain was my favorite organ. On the talking front, I had a patient in his fifties who had suffered a depression after having a stroke and losing his job. I felt like as I got deeper into his story, the level of emotional connection became more intense. And as that happened the level of caring became intense. The relationship felt so meaningful, and I wanted to be the kind of doctor who had that kind of connection to patients. That is what makes clinical work so satisfying. That and the fact that we so often can make a real difference for people with the treatments we have. On the brain front, the complexity seemed endlessly fascinating, and there was clearly so much still to discover about how the brain worked in normal and abnormal states. I knew that the intellectual thrill of exploring the brain would never grow old.
  • What research are you currently focused on?
I am searching for genes and variations in those genes that predispose people to depression and bipolar disorder. I got started with a wonderful mentor and role model, Ray DePaulo at Johns Hopkins, who began looking for bipolar disorder genes in the 1980s. I had my first experience working with him as a medical student in 1992, and eventually I decided that I wanted to focus my research on trying to figure out how changes in a person’s genetic code could lead to changes in the brain and, from there, to changes in thoughts, feelings, and behavior. I am now co-directing a project to analyze DNA sequence from the exome of bipolar disorder patients, that is, from the 300,000 or so exons that make up our 20,000 genes. The hope is to find variations in patients that are not seen, or are only rarely seen in controls. I am also on the steering committee of the Bipolar Sequencing Consortium, which brings together similar data from 15 studies with the idea that there is power in numbers. Like the NNDC, this is a highly collaborative effort that brings together leading researchers from many institutions. My other area of interest is epigenetics, or changes in the genetic material that is not part of the sequence itself. I have been working for awhile on DNA methylation, the addition of a methyl group to a nucleotide, which can have functional implications like turning the associated gene on or off. I have a grant to study whether stress can have this effect on the DNA in brain cells. We are looking at that in mice, with the idea that it might also apply to people who are stressed, such as, for example, those who are subjected to combat or sexual trauma. This change in biology might mediate the impact of stress on the development of depression.
  • What advancements in the field are you most excited about?
Genetics is what excites me the most, because I have been deeply involved in it, and also because it holds the promise of being able to put us on the path to understanding the pathophysiology of mood disorders. That, in turn, could provide new drug targets. One goal is to achieve the kind of success seen in cystic fibrosis where a subset of patients with a specific type of genetic defect respond very well to a particular new drug, ivacaftor. Another more immediate goal is to see whether people’s genetic profile can predict response to existing medications. The NNDC is working along these lines in its partnership with Assurex Health, the company that makes the GeneSight test to predict patient’s success with various antidepressants. At the same time that I very much want to see new and better options available for patients, I try to maintain a healthy skepticism as any scientist would, and especially so because psychiatry has been historically prone to embrace new thinking and methods before they have been rigorously tested and proven. In the realm of genetics, after a long period of our field not finding much of anything definitive, from about 1987-2007, we have in the last 8 years or so begun to get some clarity about genes and genetic variations that play a role in major mental illness. This has been most true for schizophrenia and autism, but there have also been some encouraging results for bipolar disorder. For example, the evidence is now overwhelmingly strong that the calcium channel subunit gene called CACNA1C has variants in it that predispose to bipolar disorder.
  • You have worked at two NNDC Centers of Excellence, Johns Hopkins & the University of Iowa. What did you take from Johns Hopkins that has helped further your career at the University of Iowa?
The first thing to know is that I was sitting in the magic office at Johns Hopkins. It was the office occupied by geriatric mood disorder expert Bob Robinson before he left Hopkins to become the Chair of the Psychiatry Department at Iowa in 1990. Surprisingly, I did the same thing from the same office in 2011. I brought with me aspects of general Johns Hopkins culture, as well as traditions from psychiatry. As a Hopkins medical student I was steeped in the “Osler Marines” culture, a reference to medical giant William Osler, the first chief of medicine there, who was dedicated to doing whatever it took to make his patients better. While this spirit is a little less prominent nationally in the setting of work-life balance concerns and resident work-hour limitations, I think it is important to encourage everyone to go the extra mile, or at least the extra inch, whenever they can for patients. As a resident I learned to take a history in the style of Adolf Meyer, the first Chair of the Hopkins Psychiatry Department and a leading figure in the first half of the 20th century. He emphasized a deep and comprehensive history of the patient’s personality and life experiences, as well as of her illness, with the idea that the former creates a context in which to understand the latter. Though time is often short, I always ask students and residents to dig a little deeper and learn a little more about their patients, because more facts mean more clarity about the formulation, and also because in the process sympathy grows and a deeper bond is forged with the patient. From my Chair when I was a trainee, Paul McHugh, I learned a systematic way to think about the nature of psychiatric disturbances, an approach described in the book The Perspectives of Psychiatry. It refers to four ways to think about patients’ problems, one grounded firmly in Medicine, called the Disease perspective, and three others grounded in psychological traditions. I handed out 200 books to the department to get people thinking about this, and I ask trainees to consider all four of these perspectives when giving an assessment of the patient, rather than simply saying “here’s the DSM diagnosis.” From Ray DePaulo, who is the Chair and the leader of the NNDC Center at Hopkins, I learned excellence requires that clinical care and research are tightly linked, since each informs the other and raises the bar for the other. I have worked at Iowa to more tightly weave the two together. For example, this year our Grand Rounds pairs a clinically oriented faculty member with a research-focused person working on similar problems. The two look at issues, like, for example, the role of stress in depression, from complementary angles.
  • Fun Fact:
I almost became a sports writer. While writing for the Yale Daily News, I briefly had that ambition. But then I spent a summer as an intern at Sports Illustrated where I covered the Los Angeles Dodgers baseball team, and I decided that metier lacked the intellectual and emotional depth that I wanted in my career. But writing has always felt compelling to me. In addition to working on plenty of grants and papers, I also wrote for a couple of years about depression for ABC Now my major writing outlet is a weekly email to my department that I call Cheers from the Chair, which highlights the accomplishments of our faculty, the history of our program and our field, all that is generally new and exciting, or whatever musings I think people might find engaging. I even occasionally mention University of Iowa sports triumphs.