Summer 2013 - A PUBLICATION OF UAMS PSYCHIATRIC RESEARCH INSTITUTE

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Former British Prime M i n i s t e r B e n j a m i n Disraeli once said, “In a progressive country, change is constant; change is inevitable.” The same could be said of the Psychiatric

Research Institute, which is going through a number of changes right now.

In May, Rick Smith, M.D., our Chairman and the Director of PRI, was named the Dean of the College of Medicine. One of the first things he did as Dean was to name me Interim Director of PRI and Interim Chair of the Department of Psychiatry. I am grateful for the confidence Dr. Smith has shown in my abilities and plan to honor his vision as a leader and educator.

I have been a member of the Department of Psychiatry faculty since 1990. I came to UAMS from the Central Arkansas Veterans Healthcare System, where I served as Associate Chief of Staff for Mental Health. I have also served as the Director of the University Hospital Division of the Department of Psychiatry, working with some of the brightest young student minds to ever come through UAMS.

During the interim, I can assure you that we will continue to serve our community with the same mission to improve mental health for individuals and families in Arkansas and beyond through the integration of outstanding education, research, clinical care and service. The exemplary faculty and staff at PRI are foundational to our success. I am grateful for their dedication and commitment.

Change is not always expected but it can be beneficial. I look forward to working with our friends and supporters in an effort to bring the highest quality of education, research and clinical care to you and all we serve.

Best wishes,

Jeff Clothier, M.D.Interim Director, Pschiatric Research Institute

John Fortney, Ph.D.

Rubenow New Head of the PRI – NW Jon C. Rubenow, D.O., who joined the Psychiatric

Research Institute – Northwest’s faculty in 2010, assumed the role of Division Chief in July, replacing Michael Hollomon, M.D.

PRI – NW works with partners, Ozark Guidance, the Care Foundation, Washington Regional Medical Center, Mercy Health System of Northwest Arkansas and Northwest Medical Center to offer the highest level of care. “It’s important for people who live in Northwest

Arkansas to be treated locally,” Rubenow said. “Before we came here, people had to go to Little Rock or farther to get the kind of treatment we now provide. Being closer to home makes a difference.”

American Journal of Psychiatry Features PRI Depression Study

Jon C. Rubenow, D.O.

John Fortney, Ph.D., Director of the Psychiatric Research Institute’s Division of Health Services Research, was the principal investigator in a recent study published in the April issue of the American Journal of Psychiatry. The study, funded by a National Institute of Mental Health grant, found that a collaborative care model using telepsychiatry along with primary care providers improves response and remission in patients with depression in rural underserved areas.

The study compared practice-based collaborative care using primary-care physicians and on-site nurse care managers at rural health centers with a telemedicine-based collaborative care model using a team of psychiatrists, pharmacists,

psychologists and nurse care managers at the UAMS to diagnose, treat and follow patients. A total of 364 patients were involved in the study, all of whom were randomly assigned to treatment for one year at one of five community health

centers in Arkansas’ Mississippi Delta and Ozark Highlands regions.

Commenting on the study, Fortney said, “It is encouraging to discover that small clinics without the resources to hire mental health specialists on site can utilize telepsychiatry to provide care for patients with depression. With this study, we have evidence to show that providers at community health centers and UAMS can come together as a group, combine our resources and better serve Arkansans struggling with depression.”

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Discovery. It informs how we understand and care for patients and what we teach our students. It is a

lynch pin for an academic department. Dr. Clint Kilts of our Brain Imaging Research Center shared with me two numbers that are important for our mission, three and 44. I will return to those numbers later. What does it take to discover new treatments and understand current treatments?

The field is at a tipping point in my opinion. The previous approach to psychiatric research was based on the American Psychiatric Association’s Diagnostic and Statistical Manual (DSM). The DSM diagnostic categories were agnostic to biology, by design. The manual was based solely on a description of observed or reported behaviors. The National Institute of Mental Health (NIMH) has launched a new initiative that seeks to understand the biology of mental illness to inform treatment approaches. It does not seek a biologic definition of one diagnosis. Rather, it seeks to understand the symptoms of mental illness and behavior that span diagnostic categories. A recent study in The Lancet revealed a common set of genetic influences across diagnoses as variable as schizophrenia, autism, and depression. This led to some controversy in May during the launch of the DSM-5.

Until very recently our treatments for psychiatric illnesses were based on the results of the study of large populations. The evidence of efficacy was based on patients sharing some diagnostic criteria irrespective of their neurobiological variations. Yet many of the treatment advances were biologically motivated. To a large extent it was serendipitous that such treatments were proven safe and effective. Yet we will have to understand the biology of individual variation to bring future innovations to the bedside. To do so will require innovation and discovery based on a new way of thinking about mental illnesses.

The UAMS Department of Psychiatry has a long heritage of seeking to place the individual at the center of treatment. We emphasize the importance of understanding the symptoms in the unique contexts of each person. Modern science is beginning to provide us with tools to add biological understanding to an individual’s symptoms. Such an approach is often described as personalized medicine. At PRI we are developing a multi-pronged framework to bring personalized medicine to the clinic and to the bedside based on a biologic understanding of each individual patient’s genetics, biochemistry and brain organization in order to select the treatment and outcome.

A recent story in the New York Times has created a stir that illustrates one aspect of the future we envision. The story reports on the use of advanced brain imaging to identify biomarkers that reliably predict how individual patients will respond to different kinds of treatment. With genomic testing, similar work will guide therapy choices, improve outcomes and develop more effective treatment options. Version 1 genomic testing is already in use for helping patients with treatment refractory depression.

We are not there yet, it will require discovery of how treatments work as a function of each patient’s unique genetic and biological background. So how do we advance our knowledge? How do we discover? Such discoveries are in the early stage and clearly dependent on commitment from the National Institutes of Health (NIH). Health-care insurers and dwindling pharmaceutical companies focusing on psychiatric medication development are not viable partners.

Through the NIH grant mechanism, a small percentage of researchers have the opportunity to delve into the biology of behavior to discover new insights that lead to new treatments or the refining of old treatments. Such NIH grants are also the engine of academic promotion. Assistant professors are expected to show they are capable by becoming independently funded through successful applications for

Discovery is at the Center of PRI’s Approach to Care By Jeffrey L. Clothier, M.D.

DiscoveryPatie

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Education

grants. This is a form of peer review. Most assistant professors are appointed in their late twenties or early thirties. The promotion and tenure process gives them seven years to prove themselves. If they do not, they are not renewed and the previous investment is lost. This is where the two numbers given in the first paragraph are important and provide an opportunity for action.

The first number, three, is the percentage of the NIH grant funding that goes to investigators under the age of 40. This is a big change over the past three decades as the age of distribution of academic researchers has become increasingly younger than the age distribution of NIH-funded researchers. The second number is 44. This is the average age for an investigator’s first major independent NIH grant, the RO1. These changes have made it more difficult to invest and develop a next generation of psychiatry researchers who will provide the discovery discussed above.

So why are these numbers actionable? They seem fairly pessimistic. They are actionable because it helps identify where we should place resources to insure the future of discovery and the future of PRI. We have wonderful facilities, talented clinicians and researchers, an abundance of patients, and a highly supportive advisory board. So what is needed? By establishing endowments such as departmental chairs we have the opportunity to provide career development funds to invest in our junior faculty and to establish programs of clinical research that specifically allow us to individualize our approaches to personalized clinical care. This is how successful programs will insure their future, our future. Steering committees are formed or are being formed for our research programs. Each committee or advisory group will be expected to include one of our advisory board members so that our supporters and patrons are integrated into the research process. This will provide a platform to insure the community-academic partnership necessary to a better future of reduced burden of mental illness.

Jeffrey L. Clothier, M.D., is a professor and interim chair in the UAMS Department of Psychiatry and the Interim Director of the Psychiatric Research Institute.

Policy

Recent stories about rapid responses to medications for depression are creating a stir. One of these treatments is ketamine. Studies have reported rapid antidepressant effects of a single intravenous dose in patients with major depressive disorder (MDD). This was unexpected by some researchers. Ketamine is described as a dissociative anesthetic which was best known for its association with emergent delirium as a person comes out from under anesthesia. It has a variety of effects on neurotransmitter systems in the brain. The most relevant is the glutamate receptor system. Ketamine is a glutamate receptor antagonist. The receptor that appears to be involved is the NMDA receptor which is coupled to a calcium channel.

One theory of depression is that the glutamate system is overactive in depressive episodes. A trial of ketamine made sense at a research level. The rapidity of response many patients had was surprising. They reported rapid relief within hours of the infusion. The incidence of side effects was also very low. The effect is not long lasting; all but two patients relapsed within two weeks. However, it provides an opportunity for more enduring treatments to ‘take hold’. Most antidepressants take two to six weeks to show effect.

Ketamine offers the hope of a rapid response which provides time for the typical antidepressants to become effective. The safety of repeated dosing has recently been reported and supports a possible role of repeated ketamine for treatment of refractory depression. The Psychiatric Research Institute has used ketamine as an anesthetic in our electroconvulsive therapy (ECT) program for years. Our experience mirrors that of others who report a more rapid response to ECT when ketamine is used as the anesthetic.

There are other rapid response strategies that are being developed using other medications, some new medications and other older medications. As these become clinically available they will become part of our interventional psychiatry program that currently includes ECT, infusion therapies, and deep brain stimulation. PRI is hopeful that in the future we will be able to add other interventions to provide rapid and enduring relief to the most difficult cases of psychiatric illness.

Anesthetic Shown to Aid Patients with Depression

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PRI Receives A+ “One of our best reviews ever,” said Tracy Petty, LCSW, PRI Compliance Coordinator. The Psychiatric Research Institute’s outpatient programs received an exceptional rating from the Joint Commission in May. PRI met stringent guidelines and state-of-the-art accreditation standards for providing the

highest quality care and ensuring that all safety measures are being met. This accreditation is a nationally recognized symbol

of quality and reflects PRI’s commitment to excellence.

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At the recent national conference of the American Psychiatric Association in San Francisco, William Kindrick, M.D., 2012-2013 Department of Psychiatry Chief Resident, and his wife, Kristi Kindrick, M.D., reported that adolescent victims of “cyber bullying” and adolescents who engage in high-risk sexual behaviors are more likely to consider or attempt suicide. Using data obtained from the national Youth Risk Behavior Survey (YRBS), Kristi Kendrick, M.D., stated that cyber bullying – threats communicated via the Internet – is a greater contributor to thoughts of suicide than in-person bullying. In a separate analysis of YRBS, William Kendrick, M.D. found that teens forced into sex, those with four or more partners or those having sex before the age of 13 are more likely to contemplate or attempt suicide than their high-school contemporaries.

UAMS in Top 10 U.S. Medical Schools Producing Psychiatrists

For the last 10 years, the UAMS Department of Psychiatry has ranked in the top tenth percentile of medical schools in the United States

in recruiting students into psychiatry. Nine of the 162 graduates from the UAMS class of 2013 selected psychiatry as their specialty of choice. Four of the nine graduates joined the UAMS Department of Psychiatry as first-year residents in July.

“I enjoyed every moment of my psychiatry rotation during my third year of medical school,” said Andreya Reed, M.D., one of the new residents joining PRI. “Each day was exciting and provided a wonderful learning experience. The support and encouragement provided by the faculty and residents’ made the decision to choose Psychiatry at UAMS easy.”

Andreya Reed, M.D.

PRI Residents Present at Annual American Psychiatric Association Conference

Information on GivingBetty Tucker, J.D., Senior Development Director of PRI

(501) 526-8134 or batucker@uams.edu.

Did you Know...

PRI Memorial Garden Completed PRI’s Memorial Garden was completed in June with the

installation of five large metallic panels detailing the history of the treatment of mental illness in Arkansas as far back as the 1800s. The garden and PRI are located on the former site of the Arkansas State Lunatic Asylum. The garden was funded by a $1.05 million grant from the Arkansas Natural and Cultural Resources Council (ANCRC). The ANCRC was established by the Arkansas legislature in 1987 to manage and supervise grants and a trust fund for the acquisition, management, and stewardship of state-owned properties. The grants, funded through the state’s real estate transfer tax, are for projects that protect and maintain state-owned natural areas, historic sites, and outdoor recreation.