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The image on the computer screen is a photograph of a brain Dr. Graznya Rajkowska received from the Department of Psychiatry at Duke University where she analyzes the post-mortem brains of patients Duke has followed clinically.

The running joke in the psychiatry department at the University of Mississippi Medical Center is that Grazyna Rajkowska, PhD, married Dr. Craig Stockmeier, PhD, for his brains.

And no, even though Stockmeier is very brainy, he was born with only one brain. The joke refers to his collection of brains that he, Rajkowska, other members of the department here, and researchers at seven other universities use to study mental illness.

The scientists look at the actual brains of suicide victims who suffered from depression and other forms of psychiatric disorders and compare them to the brains of people who died from other causes.

The research has led to new insights about minute anatomical changes that characterize the brain of a person suffering from depression. Collections such as this one are rare. Rarer still are collections that have psychiatric and medical data to go along with the data that can be gathered from the microscopic analysis of the brain tissue.

Stockmeier started the collection in Cleveland, Ohio, in 1989, seeking answers to his own research questions. He wanted the actual brains so he could tell why the hippocampus region of the brain was reduced in patients with depression.
He was on the faculty of Case Western Reserve University in Cleveland when he started the collection. Ten years later, he was recruited to Mississippi. But even though he's several hundred miles away, he still directs the program.
"Cleveland has about three times the population of the metro area of Jackson, so it's primarily about the numbers available," he explained.

And the system is working well. In fact, the National Institute of Mental Health of the National Institutes of Health has continuously funded Stockmeier's collection both because of the wealth of data scientists have mined from it and because Stockmeier trains technicians so carefully in the removal of the tissue.
Every weekday, someone on Stockmeier's team checks in at the Cuyahoga County Coroner's Office in Cleveland to see what cases have come in the last 24 hours.

When a victim of suicide is identified, the team contacts the family for permission to remove the brain for research. Three months later, the team conducts a series of extensive interviews with the people who knew the victim to get a complete psychiatric portrait and medical history. The team also seeks permission to use the brains of people who died from other causes for comparison purposes.

The brains that Stockmeier collected answered his questions about the hippocampus. Serotonin is the neurotransmitter first identified as having a critical role in depression. Depression is associated with a decrease in serotonin function. Stockmeier, now a professor of psychiatry and human behavior at UMC, was among the first scientists to discover a potential mechanism that puts a brake on serotonin production in the cells of the brain stem. And he found fewer serotonin-containing fibers in the brains of depressed patients. Both findings proved crucial in the understanding of the anatomical basis for depression.

Rajkowska, professor of psychiatry and human behavior, one of the foremost neuroanatomists in the country, was one of the first scientists to show the importance of glial cells in the brain. Prior to her research, scientists thought these cells merely provided "glue" for the neurons, the major information processors in the brain. With others, Rajkowska has shown that glial cells are vitally important in delivering nutrition to neurons, and their density and number are decreased in the brains of people with depression.

This is in contrast to the brain pathology of neurodegenerative diseases such as Huntington's chorea. The anatomy of these brains is characterized by a loss of neurons but an increase in glial cells. "In these brains, there are more glial cells than normal, suggesting that the glia are compensating to support the neurons that are still alive," she said.

For the past five years, Rajkowska has been a key collaborator in a research project at Duke University — a research project that was threatened with loss of funding if they didn't address postmortem brain studies.

"The Duke study looks at geriatric depression," Rajkowska said. "They follow patients throughout their lives and compare results of those who developed depression late in life to those whose depression came early in life." Every two years, participants in the study have a thorough diagnostic workup.
"I was recruited because of my work in postmortem brain studies," she explained. The study, gathering clinical data for years, needed the final piece of information to correlate to the living record.

But in five years, only one person in the Duke study died — a problem only for pathologist Rajkowska. For the first time, she is turning to brains other than those of her husband. "The Duke study rules out the use of suicide brains, so we will rely instead on brain tissue from Emory and the University of Utah," she said.

The research of Rajkowska and Stockmeier is funded by the National Institute of Mental Health of the National Institutes of Health, the National Alliance for Research on Schizophrenia and Depression, and the American Foundation for Suicide Prevention.


May 2007

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