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.”

0812_suicide1Cheryl McCullumsmith

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.

Rapid Relief

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.”

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UAB Researchers Targeting New Ways to Define, Treat the Disease

By Matt Windsor

0812_depression_collage

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.

By Dale Short

2005_mars5Spirit scours away the orange-red dust from a clump of rock. Her small metallic arm, a spinning brush on its tip, is preparing the rock’s surface so that other devices on her robotic body can photograph the minerals underneath with a microscope and then test their chemical composition.

This Rover, a coffee table-sized machine whose name and build suggests something akin to a robotic puppy, proceeds diligently, receiving its instructions by remote, unafraid and unhindered by the punishing environment in which it works. Exploration by remote control has become commonplace these days, as work crews routinely use video hookups to safely scope out cramped or hostile environments. The big difference with this project is that the job site is some 35 million miles away: specifically, the surface of the planet Mars.

Back on Earth, UAB astrophysicist Thomas Wdowiak, Ph.D., sits at his computer terminal at NASA’s Jet Propulsion Laboratory in Pasadena, California, awaiting data on the Martian rock. Using instructions uplinked earlier by Wdowiak, a powerful instrument on Spirit is rotated into position so that it can measure the mineral content of the rock. As the measurements begin, Wdowiak, a space- exploring scientist tens of millions of miles away, becomes one of a handful of human beings who have touched the surface of another planet—at least, “touched” it as literally as possible, until some manned spacecraft takes the next step in a future decade.

Staring at the Stars

For Spirit and its twin vehicle Opportunity, the odyssey to Mars began when they were launched on separate rockets in June 2003 from Cape Canaveral, Florida. But Wdowiak’s personal journey into space began in an elementary school library in Binghamton, New York, in the 1940s; has survived Spirit’s inconvenient (but thankfully temporary) computer shutdown several days after landing; and currently shuttles him between the Red Planet and Birmingham’s Red Mountain, which Wdowiak calls home when he’s not off exploring Mars.

“One of Bonestell’s paintings was of Mars,” says Wdowiak, “and that’s the first time I was exposed to the concept of Mars as a world. Not as a planet. There’s a difference. A planet, you look at. But a world is a real place that you can stand on, can walk around in.”

At age 65, with an intense gaze, Wdowiak remains just as fascinated with exploring other worlds as he was as a child. “I’ve been preparing for this mission since I was seven or eight years old,” he says. He vividly recalls the afternoon in his school’s small basement library when he was thumbing through an aviation magazine and came across the imagined landscapes of planets, as envisioned by a painter named Chesley Bonestell, who was a cult hero of science-fiction fans and whose outer-space concepts were so eerily convincing that his art was in great demand for films of the period such as War of the Worlds.

“One of Bonestell’s paintings was of Mars,” says Wdowiak, “and that’s the first time I was exposed to the concept of Mars as a world. Not as a planet. There’s a difference. A planet, you look at. But a world is a real place that you can stand on, can walk around in.” Today, a signed print of one of Bonestell’s creations hangs on the wall of Wdowiak’s den.

To say that the young Wdowiak then began taking an interest in science is an understatement. His first project was a chemistry lab in the family basement. Fortuitously, his uncle was studying at Cornell on the GI Bill and began bringing him old, discarded supplies from the university’s laboratories—making Tommy Wdowiak arguably the best-equipped fourth-grade scientist in New York state.

By high school, his science interests had turned to rocketry, and he began creating pencil-sized projectiles fueled by household materials. His rocketry magnum opus came when he got hold of a discarded vacuum-cleaner attachment and outfitted the steel cylinder with an engine and fins. “That rocket went supersonic,” he jokes. “We thought we were taking precautions with all this stuff, at the time, but in retrospect it’s a wonder none of us got hurt.”

Then current events took over. When the Soviet Union made world headlines by launching the first orbiting satellite, named Sputnik, the 17-year-old kid with the rocket fetish was suddenly in demand as an expert. The local TV station interviewed him about space travel for its nightly news. And his high-school chemistry prof organized a gathering of the county’s science teachers so Wdowiak could bring them up to date on the mechanics of rocketry and satellites. “It was my very first classroom lecture,” he says, laughing. “I did all right.”

Identifying Mystery Rocks

2005_mars2In high school, the budding physicist Wdowiak (left) launched homemade rockets in his New York neighborhood.Wdowiak’s academic career continued at Florida State, the University of South Florida, and Case Western Reserve, followed by research stints at NASA, General Electric, IBM, and other outfits before turning to a teaching career. Along the way, Wdowiak became expert in a somewhat exotic specialty that allowed him to combine his interests in chemistry, geology, astronomy, biology, physics, and space exploration. It bears the unglamorous name of Mössbauer spectroscopy, named for German science prodigy Rudolph Mössbauer, whose discovery won him the 1961 Nobel Prize for Physics, at the age of 31.

To drastically oversimplify a complex technique: Materials reflect, and also absorb, invisible radiation known as gamma rays. A Mössbauer spectrometer can measure with tremendous precision just how the gamma rays are changed by the iron atoms of the objects they strike. These measurements, in turn, generate scientific insight into those substances’ atomic and molecular structure.

Such a technique proves very valuable in determining the composition or origin of mysterious rocks, such as possible meteorites or long-buried fossils. Wdowiak’s talent for studying meteorites using the Mössbauer technique was one of the credentials that landed him a spot on the “dream team” of researchers from around the world, known as the Athena Group, who were drafted in 1997 to help plan the current Mars mission. The team was charged with executing the ultimate scavenger hunt on the surface of Earth’s nearest neighbor—with the grand prize going to anyone who spotted evidence of life.

Martian Microbes?

The Mössbauer instrument that Wdowiak commands on Spirit and on Opportunity is only one of those vehicles’ many measuring devices, all sending back a massive quantity of data that will keep scientists busy for years, if not decades. But the Mössbauer is a crucial instrument to the mission’s quest for information on the conditions of the ancient Martian environment and whether or not life could have existed there. A basic clue as to whether the ancient environment was suitable for life could be the presence of a common mineral called hematite, which is believed to form only in the vicinity of water. Where there’s hematite, there was once water; and where there was once water, it’s possible that there may have been life.

The Mars verdict? “Hematite,” Wdowiak says, with spectroscopic assurance. And though the case for Mars’s liquid past is not yet airtight (or, more accurately, watertight), the hematite and related discoveries from the current mission are immensely encouraging to scientists such as Wdowiak’s UAB colleague, physicist Perry Gerakines, Ph.D., who coincidentally teaches a course titled Extraterrestrial Life. His recent students in that class got far more than a textbook version of the subject, including video updates from the NASA lab in Pasadena and an in-person lecture and slide show from Wdowiak during a trip home.

“One of the strongest pieces of evidence,” Gerakines says, “is that there appear to be gullies and runoffs in some of the crater walls on Mars, as if liquid has seeped out between the layers and run down the sides. Although water is not the only possible explanation for that phenomenon, it’s the most likely one.”

If there are any life forms on Mars today, Gerakines believes, they’re probably underground—and are probably single-celled microbes. There’s precedent for that on Earth, he says, where “there’s plenty of microbial life, miles underground, which manages to survive with no sunlight and very little moisture.”

The notion of bacteria in outer space might not get the public’s pulse pounding like the alien rocket ships in War of the Worlds did, but the possibility of extraterrestrial single-celled organisms is a much bigger deal than it sounds to the lay observer, according to Gerakines. Where life is concerned, that first microbial cell is apparently the hardest leap to make: “The fossil record on Earth indicates that less than a billion years ago, or about one-fifth of our planet’s lifetime, multi-celled organisms had not even appeared yet. The only life was bacteria. So in a sense, you could say that the more sophisticated life forms are relatively easier to evolve than that first big step—from lifelessness to the microbe.”

Overdosed on Dove Bars

As enamored as he is of Mars, Tom Wdowiak has a strenuous, around-the-clock relationship with the Pasadena nerve center from which the Spirit and Opportunity Rovers get their daily marching orders. Although he and his wife lived for several months in an apartment near the Jet Propulsion Laboratory (JPL) last year, he now operates remotely from his bedroom atop Red Mountain in Birmingham.

2005_mars3From his Birmingham home, Wdowiak continues his work on Martian studies.Ironically, he says, the high-security, high-tech, high-rise JPL compound is not the best place to contemplate the natural beauty of Mars or the philosophical implications of all the scientific data that’s accumulating there. “The mission operations are pretty intense,” he says. “We have strategy sessions, and then we go back to our little rooms and complete our individual parts of the process. There’s not a lot of socializing, because there’s just too much work going on. And most of the people there are 20 years younger, 30 years younger, than I am.” Moreover, he says, the fact that one’s keyboard fingers are maneuvering what’s essentially a half-billion-dollar piece of delicate equipment across rocks and craters is not exactly conducive to relaxation.

Which is not to say that NASA doesn’t try to add some homey touches for the overworked technicians. A small cart with snacks and beverages regularly makes its way through the corridors. There’s also a freezer stocked with a selection of exclusively gourmet-brand ice creams. “I never thought I’d get tired of eating Dove bars,” Wdowiak says. “But by the time I get back to Birmingham, I’m craving just a plain old popsicle.” And from a more practical point of view, the Spirit and Opportunity crews work on separate floors of the building, which are carefully color-coded, from walls to chairs, so that nobody ends up in the wrong area by mistake—which can happen more easily than you might think, Wdowiak says. “You get exhausted enough, you can get a little loopy.”

The rigors of the Rover mission prompted one reporter to ask Wdowiak if his all-day sessions at the Mars video monitors make him dream at night that he’s actually walking around on the planet. Wdowiak didn’t hesitate before answering: “I don’t have to dream about it,” he shrugged. “I’m already there.”

“A Billion Years’ Worth of Grime”

Indeed, his casual descriptions of a typical day on the Red Planet sound not like a scientific textbook, but rather like someone recounting a recent exotic vacation.

“The most noticeable thing about the Martian landscape is that there’s no vegetation,” he says. “And the sky is pink. Everything on the ground is rocks and an orange-colored dust, and there are little meteor craters everywhere. Earth would have the same kind of craters, of course, except that most meteors burn up in our atmosphere. The atmosphere on Mars is only about 1 percent as dense as Earth’s, so the meteoroids come right through it.

“The ground on Mars is covered with a billion years’ worth of grime, dirt, dust, whatever you want to call it. It’s basically powdered lava, which eventually turns reddish in the atmosphere, the same as you see in some places out West. But if you brush that dust away and grind into the rocks a few millimeters, they’re black inside—basalt, generally. In other words, igneous. Volcanic.”

“The sky is pink. Everything on the ground is rocks and an orange-colored dust. . . . It’s basically powdered lava, which eventually turns reddish orange in the atmosphere. . . . But if you brush that dust away and grind into the rocks a few millimeters, they’re black inside. . . . igneous. Volcanic.”

In fact, if the atmosphere weren’t composed of mainly carbon dioxide, with just a touch of argon, the desert-like vistas that the scientists are seeing courtesy of the Rovers’ panoramic cameras would be a nice place to take a stroll—in the daytime, at least, when temperatures in the sunshine can reach the mid-70s. Except that you’ll need to keep an eye out for the occasional dust storm, which can envelop much of the planet with wind speeds that are the equivalent of an F-1 tornado on Earth.

And you’ll need to have some seriously insulated garb on hand when night falls, because temperatures can drop to the minus 180s—a chill factor that leaves an Antarctic winter in the shade.

Wdowiak says it’s these extremes of Martian temperature, rather than any inherent mechanical flaws, that will probably force the inevitable breakdowns of the Spirit and Opportunity Rovers: “When you have materials expanding and contracting to that extent in the diurnal cycle . . . circuit boards and soldered joints and so on . . . something’s almost sure to crack, eventually. That’s what’s going to kill us. That, or the dust will gradually accumulate on the solar-power panels and attenuate the sunlight.”

But he’s philosophical about those outcomes. “It’s not very widely known, but the Rovers were built for a 90-day life span. I like to say they had a ‘90-day warranty.’ And they’ve already far, far exceeded that.”

A Hundred Billion Suns

“Opportunity is closer to the equator. . . . Spirit is farther south . . . where it’s a little colder; it has a bit of rheumatism, but it’s busy climbing the Columbia Hills. Eventually it will reach a height that will give it a view equal to looking out over Birmingham from the top of Red Mountain.”

Wdowiak says the Athena team initially considered “hibernating” one of the Rovers during the harsh Martian winter, but they found that the vehicles took well to the winters, so they’re now operating all year long. “Opportunity is closer to the equator, and it’s actually functioning as if it’s on a desert island,” Wdowiak says. “Spirit is farther south in the Southern Hemisphere, where it’s a little colder; it has a bit of rheumatism, but it’s busy climbing the Columbia Hills. Eventually, it’ll reach a height that will give it a view equal to looking out over Birmingham from the top of Red Mountain.”

What does Wdowiak plan to do for an encore when the Spirit and Opportunity are both history? For one thing, he’s excited about a new and improved robotic Mars mission, tentatively scheduled for a 2009 launch. These Rovers will be nuclear powered, making them more muscular and also independent of solar panels and their inherent limitations.

Plus, Wdowiak continues to explore, in his spare time, a pet project that has obsessed him for years. Based on many factors, he has a hunch that the most likely spot for extraterrestrial life is not a planet, but a moon. The bizarre celestial body is named Europa; it orbits Jupiter and apparently has an ice-crystal shell and a liquid center. As he notes, with water, water everywhere, could life be far behind?

The fact that the Europa search probably won’t take place in his own lifetime doesn’t seem to dissuade Wdowiak from working on instruments that will someday explore the strange moon. For him, the question of life is less a question of “if” than of “when.” “Do you know how many suns there are, like ours?” he asks. “A hundred billion. Maybe more. Think about that.”

Tracing Malaria’s Epic War with Humanity

By Matt Windsor

Lori Cormier knew she had to hurry. The young anthropologist had already seen several life-threatening malaria infections during her time among the Guaja hunter-gatherers of the Brazilian Amazon. Seizures were not a good sign.

0712_malaria_cycleMalaria requires both mosquito and human hosts to survive. Mosquitoes ingest the parasite that causes malaria when they bite humans or wild primates; the parasites reproduce in the mosquito and travel to its salivary glands, where they infect the mosquito's next victim. In these human or wild primate victims, the parasites enter and reproduce in liver cells, then place male and female versions of themselves in the bloodstream, waiting for the next mosquito bite to start the process again.

Click image to see larger version and see "A Vicious Cycle" for more on the process.


“I had brought a few medical supplies with me into the field, and when people were very ill they would come to me,” says Cormier, who was a doctoral student studying the Guaja language and culture in the late 1990s and is now an associate professor in the UAB Department of Anthropology.

Reality Bites

Malaria is caused by a cunning parasite with a complex lifecycle; in fact, it bears an uncanny resemblance to the villains in the Alien movies. Here’s how it works: A female Anopheles mosquito, carrying the parasite Plasmodia in its salivary ducts, bites a human. The parasites move into the person’s bloodstream, where they migrate to liver cells and reproduce. A few days later they emerge in the thousands from each cell and invade nearby red blood cells, where they grow and later burst out again to infect new red blood cells. The process causes high fever, convulsive chills, anemia (not enough red blood cells), and flu-like symptoms, usually 10 days to four weeks after the infection begins. (See “A Vicious Cycle,” below.)

When a five-year-old child was rushed to her hut one morning with seizures, Cormier sprang into action. “I had aspirin, but that doesn’t work fast enough,” she says. “So I ran to the river and soaked a blanket in cold water to try to cool her.” Eventually, the child recovered, but for the rest of her life the fever would threaten to return.

Studying the Environment’s Impact on Health

By Joe Rada

0712_gohlkeJulia Gohlke is studying the health effects of climate change in urban and rural areas, including how ambient temperatures affect mortality and premature births.When Julia Gohlke, Ph.D., moved to Alabama in 2010, she found herself on the front lines of a disaster. The Deepwater Horizon oil spill had just occurred, creating a primary health concern for the Gulf Coast states. So Gohlke, an assistant professor in the School of Public Health’s Department of Environmental Health Sciences, jumped right in to help with spill-related research. “I worked with a fisheries group to review the process used to determine seafood safety,” she says, glad for the chance to contribute something positive during that unfortunate situation.

Around that time she also met Fulbright fellow and UAB doctoral student Dzigbodi Doke from Ghana in West Africa, and the pair put their firsthand knowledge of the oil disaster to good use. “We conducted a seminar in Ghana on lessons learned from the spill,” Gohlke says. “A large group of stakeholders there is interested in the burgeoning deepwater oil industry in the Gulf of Guinea. That opportunity led to a collaboration with several Ghanaian researchers interested in environmental issues.”