Yale psychologist Rajita Sinha started with a simple question posed to a diverse group of academic colleagues at Yale and two other universities.
"What is the role that stress plays in the loss of self-control leading to overconsumption of tobacco, alcohol and foods?"
The question led to a collaborative $23 million effort of social scientists, neuroscientists, radiologists, psychiatrists, molecular biologists and health economists to find new ways to understand and treat addictive behaviors. Six months later, the interdisciplinary quest is enabling scientists to better tackle a complex set of health, behavioral and social problems, providing a model for other cooperative scientific efforts at Yale and laboratories across the country, and yielding surprising insights into the human condition.
"This effort will have implications far beyond the targeted focus of these studies,'' predicts Sinha, professor of psychiatry.
Smoking, drinking and overeating are the top three causes of preventable death and disease in the United States. In order to tackle this huge social issue, the Yale Stress Center headed by Sinha proposed a sort of Manhattan project to study the relationship of stress to the abuse of tobacco, alcohol and food. The center recruited 16 researchers from Yale, Florida State and the University of California-Irvine, and applied for funding from the National Institutes of Health (NIH) under its Roadmap initiative, which is designed to foster interdisciplinary research. The NIH received more than 100 such proposals, but the Yale led-proposal was one of only nine to receive funding.
The focus on a simple question - the impact of stress on self control - immediately opened up a host of research opportunities. For instance, many of the researchers share an interest in the study of compulsion, which drives addicts to smoke, drink or eat regardless of consequence.
Jane Taylor, associate professor of psychiatry at Yale, has studied the neurobiology of compulsive habits for many years. She has found that a brain region called the nucleus accumbens is key for the creation of emotional habits and compulsive behaviors. The prefrontal cortex can regulate the nucleus accumbens, and thus inhibit compulsive behaviors.
"The flip side of compulsion is a loss of control,'' Sinha notes.
And that territory of the brain is fertile intellectual ground for Yale neurobiologist Amy Arnsten.
Arnsten is a one of the world's experts on the prefrontal cortex, the seat of higher cognitive function and also the area of the brain that plays a key role in impulse control. Several labs have now shown that chronic stress exposure can actually lead to structural changes in the brain. Stress unleashes a biochemical cascade that short-circuits the prefrontal cortex's ability to moderate impulses. With sustained stress, scientists have learned, the brain actually loses gray matter in the prefrontal cortex, a finding that suggests chronically stressed individuals would find it very difficult to rein in their impulses and, say, turn down a cigarette or a drink.
While it may be difficult, it is possible for addicts to learn to control those impulses, theorizes consortium member Roy Baumeister, the Francis Eppes Eminent Scholar and professor of psychology at Florida State University. Baumeister has long been interested in addictive behaviors in adolescents and is now studying whether the damaging effects of stress can be repaired by mental exercise. His experiments are testing whether college students can actually learn to improve self-control - a skill sorely needed by those seeking to quit or limit smoking, drinking and eating of rich, fatty foods.
Researchers are also looking to find new drugs to curtail addictive behavior, and Arnsten's lab is again playing a central role. Arnsten has identified multiple ways that stress leads to dysfunction of the prefrontal cortex. She has found that medications that inhibit stress pathways in the prefrontal cortex may help people have better control over their thoughts and actions. For example, the drug prazosin is currently being used to treat patients with post-traumatic stress disorder. Another drug, carvedilol, is being tested by Dr. Sherry McKee, an associate professor of psychiatry at Yale. McKee is exploring whether carvedilol can help people resist the urge to smoke when they are stressed.
Another important brain pathway is being studied by Daniele Piomelli, the Louise Turner Arnold Chair of neuroscience and professor of pharmacology and biological chemistry at the University of California-Irvine. Piomelli is investigating whether stress early in life disrupts the endocannaboid system, the molecular pathway activated by marijuana that also seems to help animals deal with stress. The disruption of this system during adolescence may lead to problems handling stress as an adult, Piomelli theorizes.
Piomelli and Arnsten are collaborating to test his ideas about endocannaboids. The hope is that manipulating this pathway may not only lead to new therapies to help treat addiction, but create a new generation of non-addictive painkillers as well.
"The researchers in the consortium are engaged in genuine collaboration, learning about differing perspectives, and combining talents to facilitate discovery," Arnsten says.
For instance, Piomelli's research on early life stress dovetails with the investigations of Yale researchers
Dr. Hilary Blumberg, associate professor of psychiatry and diagnostic radiology, and Dr. Linda C. Mayes, professor of pediatrics and psychology and the Arnold Gesell Professor of Child Development at the Yale Child Study Center.
Mayes has long been interested in why adolescents raised in stressful environments are more likely to engage in risky behaviors, such as alcohol and drug abuse. Mayes and Blumberg have decided to use imaging technology to examine how stress alters brain development - and increases risk of addiction.
There is another side of the issue: What effects do addictive substances have on the brain?
This question helps drive Sinha's own research.
"We have been studying whether and how alcohol, nicotine and maybe even rich, fatty foods may affect stress and compulsions," Sinha says. "They seem to weaken stress regulation pathways or our ability to ‘de-stress' and simultaneously activate craving pathways."
In other words, the substances further batter systems already under assault by chronic stress. Scientists like Sinha have begun to provide an outline of a devastating feedback loop: Stress creates conditions in which compulsion to consume addictive substances can take root. The substances themselves further decrease an individual's ability to combat compulsion. Brain imaging experts like Dr. Alexander Neumeister and Dr. Marc Potenza, both associate professors of psychiatry and diagnostic radiology at Yale, are examining these processes in the brain using individuals suffering from addictive habits and healthy volunteers.
It is these types of insights that can change social attitudes and policies toward addictions, help individuals find better ways to manage stress, and create new treatments and drugs to curb addictive behavior, Sinha says.
The same collaborative approach could also lead to similar insights into other chronic disease states, cancer, heart disease or diabetes, she said.
"By linking investigators from different disciplines, we are creating the structures and organization to let investigators interact, learn from each other and push the process of science and discovery forward in a more efficient manner," she says. "Right now, they are often too busy in their own silos. This is another way to look at complex diseases."
The work above was funded, fully or in part, by the Yale Clinical and Translational Science Award (CTSA) grant from the National Center for Research Resources at the National Institutes of Health.
Contact
Bill Hathaway
203-432-1322
Click here to view the original article.