Brain Changes Seen In People With Depression

Dr. Grazyna Rajkowska, associate professor of psychiatry and human behavior, looked at the region of the brain known as the prefrontal cortex. This "gray matter" -- located just behind the forehead -- is responsible for higher intellectual functions and regulation of emotional and motivational behavior.

The results of Rajkowska's work appear in the lead article in the May issue of the journal, Biological Psychiatry.

Earlier work that scanned the same region of the brain in living subjects indicated that this region of the brain was smaller in those who suffered from depression than in the brains of those who did not.

"The decrease in volume was an indication to me that something was unusual in the cell architecture and that there might be cellular changes in that area," she said.

The changes Rajkowska noted were in neurons and glial cells. The neurons are the basic unit of the brain, transmitting and receiving signals and processing information. Glial cells form the "support system" for the neurons. They don't transmit impulses, but they control the nutrients the neurons get from the blood, are active in the immune response and generally facilitate the work of the neurons. While other scientists pinpointed changes in glial cells in one region of the cerebral cortex in individuals with depression, Rajkowska's work at the same time found changes in both types of cells in three different regions of the cerebral cortex.

Rajkowska's career has been spent examining changes in the brain in several types of psychiatric and neurological illnesses including schizophrenia, manic-depressive illness and Huntington's disease. Her current research in depression showed there are fewer glial cells in the brains of people with depression and that the neurons in the same brains were smaller than normal and lower in density. The opposite is true in neurodegenerative diseases such as Huntington?s chorea. "In these kinds of brain illnesses, neurons die, and the glial cells try to compensate and support the neurons that are still alive. That's why there are more glial cells in diseases classified as neurodegenerative," Rajkowska said.

Further studies will show whether the changes in the brain were the result of depression or anti-depressant medication prescribed to help depression.

To sort out that information, Rajkowska will work with neuroendocrinolgist Dr. Garth Bissette, professor of psychiatry at UMC, who has an animal model for depression in rats and will look at rats given antidepressants and those not given medication.

"If the structural changes we?re seeing do, in fact, coincide with clinical depression, we could be looking at a major step toward designing better antidepressants," she said. "We will certainly know more about the mechanisms of depression."

Rajkowska's work also points to depression as more than a "chemical imbalance," as it's been called. "It's actually a complicated physiological illness that involves both brain structure and biological processes," she said.

Rajkowska uses brain tissue collected by Dr. Craig Stockmeier of the University Hospitals of Cleveland and Case Western Reserve University in Cleveland, Ohio. There, researchers seek permission from the families of suicide victims for donation of brain tissue and an interview. By asking certain key questions, the interviewer determines if the person who committed suicide also had major depression or another type of psychiatric illness. In addition, donations of brain tissue are sought from people who had no history psychiatric illness.

"These control subjects are valuable standards for comparison with the suicide victims," Stockmeier said. "They enable us to identify abnormalities in the brains of people with clinical depression."

Rajkowska and colleagues Stockmeier and Dr. Greg Ordway, associate professor of psychiatry and human behavior at UMC, share the brain tissue to examine several biological features in a number of brain regions. While Rajkowska focuses on changes in neuroanatomy in the brain, Ordway and Stockmeier examine two neurochemicals, norepinephrine and serotonin, that appear to be key to regulation of mood and suicidal inclinations. This collaborative research receives financial support from the National Institutes of Health and private foundations including National Alliances for Research on Schizophrenia and Depression and the American Foundation for Suicide Prevention.

Rajkowska will be a panelist at a satellite symposium organized by the National Institute of Mental Health this month during the annual meeting of the American Psychiatric Association. She was invited as one of the five leading scientists in the country on the neurobiology of mental disorders.

It was Rajkowska's work that allowed scientists for the first time to identify characteristics of overlapping layers of brain tissue in the cerebral cortex. "The layers are formed at different points in the brain?s development, and I found cellular characteristics that distinguish one cortical layer from another. Now, when you look for cell changes, you can know at what period of development the changes occurred."