FEATURE — Spring 2008

For Professor Linda Cottler, Ph.D. ’87, the intervention part of studies is most satisfying. Her team of researchers helps people improve their lives: through education; HIV, STD, and hepatitis testing; medical intervention; nutrition information; and peer counseling, among others.

Addiction Research: Exploring Issues Hidden Below the Surface

University researchers Linda Cottler and Laura Bierut search for those suffering from addiction, as well as for the biological, psychological, and environmental clues behind the widespread disease and despair.

By Candace O ’Connor

Standing on street corners, sleeping in vacant buildings, or languishing in prison cells are thousands of St. Louisans, addicted to crack cocaine, who are lost and too often forgotten. For every one who finds the path to treatment or cutting-edge medical studies, many others do not—and never have the chance to make a better life. That is why Linda B. Cottler keeps the photo of an iceberg—with a small piece above the water and a giant portion below—to help explain what her job entails, what skills she needs, and why she feels so passionate about doing it well.

“Observation, persistence, doggedness, understanding—those are the things that epidemiology requires,” says Cottler, professor of epidemiology in the Department of Psychiatry. “If you look only at the tip of the iceberg, you are not reaching the people who need the most assistance. Many barriers keep people who have symptoms and problems from receiving the treatment they need.”

Her job—and her life’s mission—is to track down invisible people in the community such as prostitutes, cocaine addicts, and heavy drinkers, who often have concurrent problems: sexually transmitted diseases (STDs), HIV/AIDS, depression, or Hepatitis C. By inviting them to participate in a study and then tabulating their responses, she and her team of researchers can do the important epidemiologic work of tracking the prevalence of an illness within a given population. And that is just the beginning.

“Many epidemiologists stop with counting behaviors,” she says. “But when we see targeted populations of hepatitis, HIV, or high-risk behaviors, we then develop interventions designed to reduce or stop them altogether.”

The intervention piece is most satisfying of all, Cottler adds. Her team helps people improve their lives: through education; HIV, STD, and hepatitis testing; medical intervention; nutrition information; peer counseling; transportation to job interviews; and a free clothes closet. For many, it is a transformative experience. They may stop drinking or start using condoms; they may stop trading sex, cut back on their crack usage or quit altogether.

“They come to us and say: ‘You helped me so much,’” says Cottler. “One lady just came back last week and said, ‘Doc, I want you to meet my fiancé. I’m sober and clean, and I’m getting married. Thank you for the opportunity to change my life.’”

Improving clinical care
For Cottler’s latest project, she and her research team are taking part in an extraordinary nationwide initiative, announced last September: the NIH-sponsored Clinical and Translational Science Awards (CTSA) program, which aims to improve clinical care. Washington University received $50 million in CTSA funds and, in collaboration with other regional institutions, has created the Institute of Clinical and Translational Sciences (ICTS). One goal of the institute is close to Cottler’s heart: fostering partnerships between academic institutions, health providers, and the community, in order to improve the health of area residents.

Cottler heads the community engagement piece of the ICTS, and her team has jumped enthusiastically into planning a program that is broader in scope than any previous effort. Soon they will initiate a two-pronged approach to connect the community with School of Medicine studies. One arm, HealthStreet, will be located in the Forest Park Southeast neighborhood, and the other will be street-based outreach.

“Whether a person has Alzheimer’s, obesity, heart disease, prostate cancer, or addictive behaviors, we will be able to directly link them to medical school studies,” says Cottler. “Before we had to turn away 90 percent of potential subjects because they did not fit our study criteria.”

If it sounds as though they are hunting for clinical “guinea pigs,” she says that is far from the truth. In fact, they are giving people unprecedented access to the latest research initiatives and critical services they may not know about, such as mammograms, anti-smoking classes, health fairs, or other screenings. Eventually, HealthStreet will also partner with other University schools and departments—such as social work, law, and business—to bring more services to the community.

An issue of fairness
When Cottler was growing up in St. Louis, her family stressed fairness, and her own belief in that principle has only intensified through the years. “There are too many disparities in research, with the population most at risk for many diseases being the least represented in studies,” she says. “Why should some people have opportunities that others do not?”

Addiction Facts:
Despite the passage of time, addiction to various substances is still a major U.S. public health problem. Although smoking has greatly decreased in recent years, 24 percent of Missourians light up, particularly the mentally ill and imprisoned. Tobacco-related illnesses are still the number one cause of death in this country, while alcohol-linked problems are number three.

Illustration:© Fotosearch

After high school, she trained as a nurse, working in pediatric neurology at St. Louis Children’s Hospital, and soon made her way to Boston where she shifted into a new career. Earning her master’s degree in public health, she was fascinated by research she did for the Slone Epidemiology Unit at Boston University. When she heard of a major study in her own hometown led by Lee N. Robins, Washington University’s well-known professor of social science in psychiatry, Cottler quickly applied to become its project coordinator.

That project—the Epidemiological Catchment Area (ECA) study—was a landmark in medical research: the largest survey ever undertaken of mental illness in the general population. During Cottler’s first week on the job, Robins saw her potential and advised her to get a doctorate. Soon Cottler was taking courses in the University’s sociology department, while working full time and—with her husband Matt—raising three daughters. She joined the psychiatry faculty in 1988 just after finishing her dissertation.

Adaptive intervention
Since that time, she has explored the relationship between substance abuse and the risk for HIV/AIDS, and developed assessments to measure those behaviors. An active researcher, with more than 150 published articles and chapters to her credit, she has received University awards for mentoring and the W. Scott Johnson Award for distinguished service from the Missouri Public Health Association. In 2007, she was named president-elect of the American Psychopathological Association for 2010; in January 2008, she won an inaugural Distinguished Community Service Award from the School of Medicine.

One innovative 1990s study, which she did in conjunction with the St. Louis City Health Department with funding from the National Institute on Drug Abuse (NIDA), established an earlier version of HealthStreet. Team members engaged people on the street in conversation about substance abuse, heavy drinking, and HIV; they invited them to come to a community-based site where participants could enroll in studies that randomized them either to standard or to enhanced, peer-delivered interventions.

By the time the study ended 18 months later, the team had achieved an unheard-of 96.6 percent completion rate among a population thought to be unreliable and non-compliant. The team also had strong success within the enhanced group at modifying crack use. But the women had a much harder time changing their sexual behaviors.

So Cottler got a grant from NIDA and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and enrolled 850 women who drank heavily or used crack cocaine—once again with a high completion rate. This time she and her team added a well-woman exam to the mix and began to see some reductions in high-risk sexual behaviors. But still the NIDA and NIAAA studies showed one thing clearly: The most recalcitrant women were those who traded sex for drugs.

There also was one surprising result. “While 2 percent of the women tested positive for HIV, more than one-third were positive for Hepatitis C,” she says. “So in St. Louis our major health problem is Hepatitis C, and we never knew about it, because the public health departments don’t do this testing.”

In a new study, still ongoing, Cottler is recruiting women from the city’s drug courts and randomizing some to a staff peer who has emerged from the same kind of life herself. This “sister” helps women by providing 40 hours of help in a 10-week period: listening to them, counseling them, and taking them places assigned by the judge.

Overall, the goal of Cottler and her staff is “adaptive intervention”—tailoring interventions to individuals based upon their histories, risk factors, and readiness to change. Finding the factors that predict change—whether they are genetics, brain structure, or environment—is the next phase of this public health model.

Cottler has earned the trust of the men and women she studies. In area prisons, where she conducts interviews, offenders now hail her by name. She sees their despair, as they wonder whether they are doomed to a life of chaos and addiction. “We want them to believe in themselves,” she says, “and to realize that someone cares enough to help them make new lives.”

To unravel the tangle of addiction, Professor Laura Bierut and collaborators—experts in molecular genetics, statistical analysis, and behavioral assessment, as well as staff of the Genome Sequencing Center—are engaged in several important studies.

Genetic Detective Work: Laura J. Bierut

Sometimes Laura J. Bierut feels like the gumshoe in a thriller that has an exciting, edge-of-your-seat plot. The novel has a villain—addiction in all its forms—and victims by the millions: alcoholics, drug users, and smokers, whose lives have been destroyed or lost. An unsavory subplot, involving a cover-up by tobacco companies, adds a twist to the story. And there is plenty of good, old-fashioned detective work, as Bierut undertakes research that will uncover who has the genetic predisposition for developing addictive behavior.

“I have the best job in the world,” says Bierut, professor of psychiatry. “The study of addiction involves so many interesting aspects—politics, big business, genetics, insurance companies—and they all come together in this incredible story.”

Bierut, M.D. ’87, became intrigued by psychiatry during a clinical rotation in medical school, when she was first exposed to people with severe mental illness. Then, during her psychiatry residency, she found a mentor and friend in the late Theodore Reich, the Samuel and Mae S. Ludwig Professor of Psychiatry and professor of genetics at the School of Medicine. “He had a vision of the future: bringing genetics into psychiatry,” she says, “and he started many of his studies long before the genetic revolution that we talk about now.”

Of course, people have known for centuries that addiction runs in families, she adds. Even the ancient Greeks had a saying: “One drunkard begets another.” But how much is biologic predisposition and how much the environment in which children are raised? Over the last 50 years, it has become clear that both factors count. Complicating the picture are differences in temperament, with some people more cautious by nature and others more novelty-seeking.

To unravel this tangle, Bierut and her team of collaborators—experts in molecular genetics, statistical analysis, and behavioral assessment, aided by the staff of the Genome Sequencing Center—are engaged in several important studies. They are targeting alcoholism as part of the national Genes, Environment, and Health Initiative (GEI), sponsored by the National Institutes of Health, in which investigators are studying a range of illnesses, such as diabetes and lung cancer. All will survey the genome for gene associations and use new techniques to study environmental factors.

In another ongoing study, Bierut and her colleagues are trying to understand genetic differences between the majority of smokers who are addicted to the habit and the tiny minority—probably 15 percent—who smoke socially but never get hooked. “This is where our best genetic findings have been,” she says, “because all of these people are being exposed to nicotine, yet there is this small group who could give it up at any time.”

On the alcoholism front, she is working on one long-running, multi-center study to look closely at risk factors for the disease across several generations. Another targets cocaine use and risk factors within the drug-addicted population. She is particularly interested in preventing cocaine addiction among the children of users—and, she says, the addicts themselves feel the same way.

“All of the subjects I have ever studied know that addiction is not good, and they don’t want their children to follow the same course. That is why they participate in these studies,” says Bierut, who has children ages 14 and 11 herself. “They understand their genetics better than anyone [else] does.”

Within the next five years, she predicts, scientists will have a strong understanding of the genetic links to addiction. And how do we use this information? “Overall, we continue education programs, taxation, and public health campaigns,” she says. “We continue to urge children to avoid smoking and to delay drinking until they are past their teenage years, when the still-forming adolescent brain is more prone to addiction.”

For the already-addicted, Bierut hopes that her discoveries may help pharmaceutical companies develop treatments that are much more effective than current drugs and patches at blunting people’s responses to addictive substances. Using an individual’s genetic information, physicians can also personalize their medical approach: targeting their intervention more precisely, choosing drugs they know will work.

“We also will be able to move into a new era of prevention, focusing on people whom we know are at risk,” she says. “We can say: ‘You are at risk, and what does this mean for you? Please don’t start smoking, because if you do, you will go down that path to addiction very quickly.’”

Candace O’Connor is a freelance writer based in St. Louis and author of the history book Beginning a Great Work: Washington University in St. Louis, 1853–2003.