Indiana University Research & Creative Activity

Mind/Brain

Volume 30 Number 2
Spring 2008

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Andrew Chambers
Andrew Chambers
Photo by Rocky Rothrock, IUSM Office of Visual Media, IUPUI

brain neuron

Altered States

by Mary Hardin

Addictions and mental illness often go hand in hand. According to the American Psychological Association, at least half of people with bipolar disorder, schizophrenia, depression, or anxiety disorders also have some sort of addiction.

Andrew Chambers wants to find out why.

Chambers is an investigator in the Indiana University School of Medicine Institute of Psychiatric Research. His research on the ventral striatum, an obscurely named, pinball-size area deep in the brain that governs motivation, may change the way mental illness and drug addiction are viewed and treated.

"The dogma is that people with mental illness are self-medicating, the idea that a mentally ill person will use a drug as a way to fix problems," says Chambers, the Raymond E. Houk Scholar and an assistant professor of psychiatry at the IU School of Medicine. He believes that long-held belief is an oversimplification; his hypothesis is that schizophrenia and addictions "are part of an integrated neurobiology."

"Prior studies focused on the notion of self-medication. I'm looking at a different hypothesis," Chambers says. "Perhaps drug use in the mentally ill has nothing to do with whether the drug is beneficial, maybe it's because people with mental illness are more likely to get addicted, even though addictions usually produce great harm. I believe the addiction process is accelerated in the context of schizophrenia."

During his third year of medical school at Duke University, Chambers began looking at nicotine and schizophrenia. Eighty percent of people with schizophrenia smoke, he notes. Conventional wisdom would indicate the smokers were getting some cognitive benefit, but that theory needed to be tested. It was while he was doing this research that Chambers began to look for a potential neurobiological connection between mental illness and addiction as a general disease process involving many drug types.

"It was a simple idea, and I thought surely I could find a paper that had already described it, because schizophrenics not only smoke, they also use more drugs of many categories," Chambers says. "Rates of alcoholism, cocaine addiction, and marijuana use are all greater [among schizophrenics] than in people without schizophrenia. Could one [addiction or mental illness] accelerate the other or predispose a person to the other?"

There was no medical literature examining this concept, so Chambers embarked on the research using an animal model of schizophrenia developed at the National Institute of Mental Health. While in medical school in the mid-1990s, Chambers learned to duplicate the model and test its responsiveness to nicotine and other drugs.

Few people had examined the idea that mental illness and a propensity for addictions could be caused by the same brain alterations. Chambers' research and the resulting paper, published in 2001 in Biological Psychiatry, were met with resistance because of the prevailing theory of self-medication.

During his psychiatry residency at Yale University, while rotating through various wards, Chambers observed that almost all the patients seen for mental illness also had an addiction. The concurrent rates were so high it could not be coincidental. Also, he observed that it was difficult to say the patients were "self-medicating" because their substance use made them more ill. Often they ignored medical advice and did not take prescribed psychiatric medications that would actually improve their conditions.

Chambers research had shown that addiction vulnerability--how easily an individual becomes addicted--was greater in the schizophrenic rat models. They not only had a greater propensity to acquire cocaine addiction but it was harder for them to stop, and they had a greater susceptibility to relapse.

"These two observations--one from my clinical experience and one from my preclinical research--started me off on a series of studies of schizophrenia and addictions," Chambers says. "The importance of that is not only so better treatments can be developed for people with dual diagnosis, but to highlight the fallacy of our division of clinical training and treatment cultures. The fact that there is a division in the care of addiction and mental illness is not helpful to patients. Mental health treatments and addiction treatments should be intertwined. Most psychiatrists should be addictionologists."

That latter view--that psychiatrists should also be specialists in the medical treatment of addiction--is controversial. It would require a significant restructuring of the way psychiatrists are educated and trained. But Chambers is firm: "Addictionology should be a core part of psychiatry," he says with conviction.

As director of the Laboratory for Translational Neuroscience of Dual Diagnosis and Development at the IU School of Medicine and assistant medical director of the Indiana Division of Mental Health and Addiction, Chambers has two missions: to help change the status quo in psychiatric training and to understand how the neurocircuitry of addictions overlaps with that of other mental disorders. It isn't just people with schizophrenia who have a propensity for drug addiction, he says.

"It's also true for PTSD (post-traumatic stress disorder); that's in part why soldiers frequently come back from combat with addictions. It's true for people with bipolar disorder, depression, and certain personality disorders. Why? Because the parts of the brain that cause these conditions are also involved in the addiction process."

Chambers' research also considers the adolescent brain and the developmental phases it undergoes. Young adulthood is a time of onset for many mental illnesses. He believes there are important clues in the development of the brain's propensity to addiction as well.

"The literature is becoming increasingly clear that people acquire addictions as adolescents or young adults," he says. "Addiction may be a developmental disorder of adolescence, just like schizophrenia. It tends to have onset and accelerate during late adolescence and young adulthood. Why would adolescence be a critical period of addiction vulnerability?

"There is a key part of the brain that undergoes rapid development during adolescence," Chambers continues. "The prefrontal cortical area that projects directly into the ventral striatum. When that part is changing in adolescence, it is not functioning correctly, or rather, not maturely functioning."

The common thread underlying addiction vulnerability appears related to the ventral striatum--the area of the brain that guides motivation. In patients with dual diagnosis, malfunctioning brain areas like the prefrontal cortex, amygdala, and hippocampus all feed into the ventral striatum. In teens, the prefrontal cortex of the brain is simply underdeveloped.

"In all these conditions, you have immature or malfunctioning brain areas that all project into the ventral striatum. But the ventral striatum is also where many brain changes underlying addiction occur. So across vulnerability states, the addictive effects of drugs in the ventral striatum may be more profound," Chambers explains.

Chambers' theory describing how adolescent neurodevelopment predisposes teenagers to addiction vulnerability, published in the American Journal of Psychiatry in 2003, has since been supported in numerous animal studies. He now seeks to expand the empirical evidence that mechanisms of addiction and mental illness are integrated.

"If you look at both these diseases through the same lens, you can see they are related," he says.

His current research explores dopamine, a neurochemical involved in schizophrenia and addiction, and the normal functioning of neurons in the prefrontal cortex and ventral striatum. He also is working on methods for understanding how the prefrontal cortex interacts with the ventral striatum, whether in the context of addictive drug use and/or mental illness.

"Addictions hurt and kill more people than everything else combined," he says. Understanding addiction can impact everything from accidental deaths, to child neglect and abuse, to public health issues such as cancer, obesity, and heart disease.

A four-year member of the IU School of Medicine faculty, Chambers is a 2005 recipient of a Career Development Award from the National Institute on Drug Abuse and a 2006 recipient of the American Psychiatric Association/AstraZeneca Young Minds in Psychiatry International Award. At the age of 38, Chambers has many years to make an impact on the way medical education approaches psychiatry and addiction treatment.

Mary Hardin is media manager for the Office of Public & Media Relations at the IU School of Medicine.