UAB Magazine Weekly - Features on Research
Health Informatics Advances Research and Health Care
By Tara Hulen
What if a cure for cancer already exists, but it is buried on a hard drive in a research lab?
Every year, drug companies test untold thousands of new compounds, clinicians turn up intriguing clues from patient tests, and investigators reveal novel targets to attack disease. “But that data needs to be analyzed, and the quantity of it is overwhelming,” says Jonas Almeida, Ph.D., director of UAB’s new Division of Informatics. The division was formed in 2011 to develop new methods to extract meaning from research findings—and give clinicians access to new tools for care.
In July 2012, the UAB team launched a first-of-its-kind medical app known as ImageJS. The program runs in an ordinary Internet browser, which means that it can be used anywhere and won’t be blocked by hospital security software. "We created a new kind of computational tool that promises to make patient data more useful where it's collected,” Almeida says. (Learn more about ImageJS in this story from UAB News and download a copy in the Google Chrome Web Store.)
In its first iteration, ImageJS allows pathologists to drag laboratory slides into the browser to get a quick analysis of cancer cell growth. New modules are already in the works that let the software tackle other tasks, and Almeida says he hopes clinicians will adapt the code to expand its capabilities still further. The lessons learned developing this app have since inspired an ongoing initiative in the Division of Informatics for data mining of the Cancer Genome Atlas, he adds. This NIH public repository of patient and tumor data has generated over 300,000 data files, a number that doubles approximately every seven months.
UAB Researchers Say Diet Plays a Key Role
By Matt Windsor
Investigators at UAB are pursuing several exciting new ways to treat depression by targeting the neurotransmitter glutamate. (See more in part 1 of this story here.) But there is a limit to what medicines can do, cautions Richard Shelton, M.D., professor and vice chair of research in the UAB Department of Psychiatry and director of UAB’s new Mood Disorders Program. “I don’t think we can just ‘drug all our problems away,’” he says. “Another very exciting element in our research program is a search for preventive treatments.”
Obesity and Depression
Food is a major factor. “Diet-associated obesity is a key risk factor for becoming depressed,” Shelton says, “but not for the reason that most people assume. Interestingly, it does not appear to be related to how people feel about how they look. Even in cultures where extra weight is not a big deal, obesity is still associated with depression.”
In fact, obesity itself may not be the prime factor. “It seems that it’s not as much about the weight you gain as what you eat,” Shelton says. “Abdominal obesity is certainly associated with a higher risk of depression, but the balance of fatty acids in the diet seems to be even more important.” Countries that have a very high content of omega 3-rich fish in their diets have very low rates of depression, Shelton explains. In countries where people eat a lot of omega-6 fatty acids in red meat and fried foods, like the United States, depression is much more prevalent.
Faculty Profile: John Laurent, O.D., Ph.D.
By Grant Martin
From riding elephants in Thailand and diving in the East China Sea to conducting vision research in Florida and California, a career in optometry has given John Laurent, O.D., Ph.D., opportunities beyond what he ever could have imagined. But when asked to pick a favorite of his many optometric posts, he doesn’t hesitate. “I can honestly say that my current position on faculty is the best job I’ve ever had,” says Laurent, now in his second year on faculty at the UABSO. “I have been very lucky throughout my career to have a number of jobs and assignments that I truly loved.”
That’s quite a statement from a man who confesses that his early impressions of academia—and optometry practice—left something to be desired. “I hated high school,” Laurent says. “I took a year off before starting college, only to find that my feelings about school hadn’t changed.” Despite that rocky start, Laurent got a reprieve from his academic woes when he was drafted into the Army and sent to Germany to work as a clerk. Little did he know that that experience would lead him to the two professions—optometry and military service—that would define his career.
A fellow GI in Germany encouraged Laurent to pursue optometry, and when Laurent returned stateside, he discovered that his perspective on college had changed. “Coming back after the Army, the world looked so much different,” he says. Laurent went on to complete pre-optometry coursework at Wisconsin and then earned M.S. and O.D. degrees from Ohio State with the help of an Army scholarship. After a payback tour in Germany, he practiced optometry in Wisconsin but soon felt constrained by the permanence of a small-town practice. He opted to return to the military, embarking on a Naval career that would span the next 26 years and would take him to such places as Hawaii, San Diego, and Okinawa. He also made an important stop in Birmingham, where he earned a Ph.D. from the UABSO Department of Vision Sciences. It was during that stop that Laurent also met his wife Becky, a Birmingham attorney.
"It’s fascinating to see the change in students from the first time they enter the clinic to their fourth year. You see them transform from students to professionals."
After retiring from the Navy, Laurent returned to the UABSO for a residency—an experience he would now recommend to other military personnel nearing retirement. “As a retirement gift to myself, I did the cornea and contact lens residency,” he says. “I didn’t expect to learn so much, since I had been fitting contact lenses for years, but I did. It was a refreshing experience, like being a fifth-year optometry student, except in my case I was 30 years out of school.”
Since joining the faculty, Laurent says he is surprised daily by the pleasures of academic life. “Teaching in contact lens labs, teaching a business course, and conducting two research projects keeps me very busy,” he says. “But I also enjoy the opportunities to work in the faculty practice and the student clinic. It’s fascinating to see the change in students from the first time they enter the clinic to their fourth year. You see them transform from students to professionals.”
UAB Researchers Explore Causes, Prevention
By Matt Windsor
Is suicide inevitable once the thoughts begin? Many fixate on this final solution to their problems long before they carry it out. Friends, family, and doctors often can do little to change this destructive thinking pattern. Few effective drugs are available, and all therapies can take weeks to have an effect.
“After a suicide attempt, many patients are just sent home, but they’re still at risk,” says Richard Shelton, M.D., Charles B. Ireland Professor of Psychiatry and vice chair for research in the UAB Department of Psychiatry and Behavioral Neurobiology. “Or they may be admitted to the hospital for three to five days, but we know that suicidal people don’t get well in a few days.”
UAB researchers are now studying an entirely new approach—using intravenous infusions of the drug ketamine to short-circuit the cycle of negative thoughts that leads to suicide and provide a potentially lifesaving mood boost.
“Most suicide studies look at patients after they have made an attempt,” says Cheryl McCullumsmith, M.D., Ph.D., an assistant professor in the psychiatry department and president of the Alabama chapter of the American Foundation for Suicide Prevention. “We wanted to look at real patients presenting in the emergency room after suicide attempts or with suicidal thoughts.” McCullumsmith and Shelton are working with Henry Wang, M.D., and Janyce Sanford, M.D., of the UAB Department of Emergency Medicine, and a research team at Yale University on the project.
Ketamine has been used as an anesthetic and sedative for years, but newer research revealed that is also has a rapid antidepressant effect. “If you use doses that are much lower than what is required to put people to sleep, you can bring their mood up fairly rapidly,” Shelton says.
“In some people, it can seriously decrease suicidal thoughts for up to a week,” adds McCullumsmith. “That should open up a window of time to allow therapeutic interventions and other medicines to start working.”
Ketamine seems to elevate mood by boosting the synaptic connections between brain cells, McCullumsmith explains. “We’re very excited about this, because very few psychiatric medications, including none of the antidepressants, have been shown definitively to decrease suicide risk.” The only exception is lithium, which is used to treat bipolar disorder and also appears to decrease suicidality, she says. In fact, psychiatrists are now prescribing lithium along with antidepressants for some patients.
A Different Approach
"People get stuck in one way of thinking," McCullumsmith says. "I tell my patients, 'It's like you have blinders on that get narrower every week.'"
Up until fairly recently, “suicide has never been addressed as its own entity,” McCullumsmith explains. “People saw it as the end result of another condition, rather than as a separate phenomenon, but now we’re rethinking that.”
Depression is clearly a major risk factor, but it is not the only one, McCullumsmith says. “There are a lot of people who are very depressed but never suicidal, and a lot of people who are not that depressed but chronically suicidal, so there is more going on.”
One key component is the loss of cognitive flexibility. “People get stuck in one way of thinking,” McCullumsmith says. “I tell my patients, ‘It’s like you have blinders on that get narrower every week.’ Many of the people we see in the emergency room just can’t get these thoughts of suicide out of their heads, so they come in or their family members bring them in.”
Another element is hopelessness, “which is separate from depression,” McCullumsmith says. “They often go together, but not always.” The financial crisis of the past several years has dramatically increased hopelessness, she says. “You lose your job, and it creates a crisis of hopelessness, along with a loss of cognitive flexibility and a rise in impulsivity.”
Preliminary data suggests that people who are impulsive are much more likely to have a suicide attempt. The connection did not emerge in previous suicide studies because they generally focus on “clean” patients—excluding people who have a history of using or abusing drugs and alcohol. “But both increase your impulsivity significantly,” McCullumsmith says. “And people who use alcohol and drugs have a significantly higher risk of suicide attempts.”
Disrupting the Cycle
Many people think that a person who attempts suicide and fails has “gotten it out of their system,” but in fact, “once you’ve made an attempt, you’re much more likely to have another attempt,” McCullumsmith says. “Suicide attempts get very repetitive; they put a groove into people’s thinking patterns.”
Many people dealing with suicidal thoughts don’t seek help, but it is possible to escape, McCullumsmith emphasizes. Cognitive behavioral therapy helps disrupt negative thought patterns. “Antidepressants help make your thoughts less sticky, too,” she says. “They free up your brain to other ways of thinking. The combination of therapy and medicine works very well, but it can take six to eight weeks to start working.”
That’s why the ketamine study has such potential, McCullumsmith says. “If we can give people a break from these thoughts and, get them feeling better, we think we can really help.”
UAB Researchers Targeting New Ways to Define, Treat the Disease
By Matt Windsor
On September 12, 2008, bestselling author David Foster Wallace, whose 1996 novel Infinite Jest was considered one of the great works of the late 20th century, hanged himself in his California home. Wallace’s father told the New York Times that the 46-year-old writer had been severely depressed for a number of months. For 20 years, Wallace had been taking medication to control his depression, which had allowed him to be productive, his father said. But side effects had led him to wean himself from the medication in June 2007. The depression returned, and after trying several other treatments, including electroconvulsive therapy, Wallace resumed taking his initial medication, only to find that it was no longer effective. “He just couldn’t stand it anymore,” his father told the Times.