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DEPRESSION IN THE BRAIN
Broadcast beginning week of April 23, 2006

Host Dr. Peter Kramer examines new research on the biology of depression including new findings showing depression is not only a disease that affects the balance of chemicals in the brain, but the anatomy of the brain, as well. This is the latest scientific evidence confirming that clinical depression is a physical, medical illness which causes changes in the brain.

Guests include: Dr. Robert Sapolsky, professor of biology and neurology at Stanford University and the author of both popular and academic books related to stress and its effects; Virginia Heffernan, the television critic for the online magazine Slate and a contributor to the anthology "Unholy Ghost: Writers on Depression"; Dr. Yvette Sheline, associate professor of psychiatry and radiology at Washington University in St. Louis; Dr. Ronald Duman, a neuroscientist and professor of psychiatry and pharmacology at Yale University; and singer-songwriter Dar Williams, who performs and discusses her song "After All."

Commentator John Hockenberry muses on the discovery of neurogenesis - the process we've been discussing today, in which new cells, including new neurons, are born in the adult human hippocampus.

According to Dr. Kramer, there is exciting new research on the biology of depression; new findings show depression is not only a disease that affects the balance of chemicals in the brain, it actually appears to affect the anatomy of the brain, itself. These studies should quiet any remaining claims that depression is not a real illness or exists "only in the mind."

We begin with a personal account from writer and journalist Virginia Heffernan, the television critic for the online magazine Slate and a contributor to the anthology Unholy Ghost: Writers on Depression, edited by Nell Casey. Ms. Heffernan says that when she had been depressed for a long time, she had trouble distinguishing her life from her life on depression -- depression felt like part of her character. During that time in her life, she says she seemed to be on a steady path to suicide, and everything she did -- from reading a book to going to the movies -- felt like an act of desperation. After she started taking an antidepressant, she began to feel better. Then she had to put her life back together and assimilate this new idea of what it meant to be depressed. Because she had already come up with so many theories -- believing at different times that depression was everything from God's curse to a byproduct of modern living -- when she felt better on medication and therefore had evidence that depression is biological, she signed onto the idea quite easily.

We know of the damaging effects of stress on some systems of the body, such as digestion and circulation. What are perhaps less well understood are the links between stress and illnesses that affect the brain. But there have been some stunning findings in this area recently. To explore this new research, Dr. Kramer interviews one of the nation's leading experts on stress, Dr. Robert Sapolsky. Dr. Sapolsky is a professor of biology and neurology at Stanford University and the author of both popular and academic books related to stress and its effects.

Dr. Sapolsky begins by explaining that human beings are strange mammals. The stress response evolved in animals to deal with short-term crises -- such as being chased by a predator -- and involves a large physical output. People, however, turn on this response in the face of psychological stressors, such as an "orange alert." He says depression is utterly intertwined with stress. When a person is depressed, she takes the response she would have to a psychologically stressful state that she has no control over, where she feels hopeless and helpless, and decides, somewhat irrationally, that this applies to her whole life. In addition, depression can act as a stressor. A person's first four or five major depressions generally follow some kind of external trauma. However, after that, something changes, and the depressions can begin to run on their own rhythm, without an external stressor to set them off.

Dr. Sapolsky then discusses the biology of how stress affects the body. When one is stressed, the body secretes hormones called glucocorticosteroids. It's known that these can damage the nervous system, causing neurons to shrivel up or even killing them, in a part of the brain called the hippocampus. The hippocampus is essential for learning and memory. He said new imaging techniques now have allowed researchers to see that in people with recurrent depression, there is atrophy of the hippocampus. This clearly shows depression is biological. We discuss these findings in greater detail in the second half of the show

To contact Dr. Sapolsky, write to: Dr. Robert Sapolsky, Department of Biological Sciences, Gilbert Hall, Stanford University, Stanford, CA 94305-5020. Or visit http://www.stanford.edu.

Then, The Infinite Mind's Marit Haahr speaks with singer-songwriter Dar Williams, who credits therapy with pulling her out of depression and saving her life. Dar Williams' latest CD is The Beauty of the Rain, released on the label Razor and Tie.

Ms. Williams suffered from depression in college. She says she felt as if she were frozen, while everyone else was alive and living in color. She performs a song from her CD The Green World, "After All," which she wrote about that time in her life. The lyrics include the verse, "And it felt like a winter machine/ That you go through and then/ You catch your breath and winter starts again/ And everyone else is spring bound."

To order CDs or contact Dar Williams, please visit http://www.darwilliams.com/.

What exactly is happening in the brain when a person is depressed? And how and why do treatments for depression work? After a short break, Dr. Kramer interviews two distinguished researchers who are dedicated to finding answers to these questions. Dr. Yvette Sheline is associate professor of psychiatry and radiology at Washington University in St. Louis and Dr. Ronald Duman is a neuroscientist and professor of psychiatry and pharmacology at Yale University.

Dr. Sheline describes the research she conducted, which Dr. Sapolsky mentioned earlier in the program. She used structural MRI to look at the hippocampi of women suffering from recurrent depression and found the hippocampal volume was smaller in these women than in matched controls. In addition, the decrease in volume appeared to be proportional to the number of days depressed. She also found subtle memory problems in these women. We know that people with acute depression often have memory problems, but Dr. Sheline's results are surprising because these problems were found in women even when they were in remission from depression. She adds that the problems are statistically significant but may not be functionally significant. These findings are significant because they show the cumulative negative effects of depression, indicating it is extremely important to prevent and treat depression.

Dr. Duman then comments on his work on the cellular level. Not long ago it was discovered that, contrary to what had been believed, new neurons are actually born in the brain, specifically in the hippocampus. This process is called neurogenesis. Stress blocks the process of neurogenesis, so one theory as to why the hippocampus atrophies in depression is that no new cells are being born (other theories include that the cells are shrinking or being killed directly). Dr. Duman has shown that both antidepressants and ECT - electro convulsive therapy -- actually increase the rate of adult neurogenesis. Dr. Sheline says that in her studies, only untreated days of depression contributed to the hippocampal volume loss, so it does seem that, for whatever reason, antidepressant medication does prevent atrophy of the hippocampus.

With a caller, Dr. Kramer, Dr. Duman, and Dr. Sheline then discuss the impact of therapy on depression. Dr. Kramer says some studies do show that therapy can cause changes in the brain, much like medication. And Dr. Sheline adds that the combination of medication and therapy has long been known to be the most effective treatment for depression.

Dr. Kramer sums up by saying that listeners have probably heard of the chemical imbalance theory of depression, and now they're hearing of the anatomical theory, but really, these are the same theory. The kinds of cells that are being lost in the brain, are, we think, the same ones that relate to chemical transmission.

To contact Dr. Sheline, please write to: Dr. Yvette Sheline, Associate Professor of Psychiatry Radiology, Washington University School of Medicine, Department of Psychiatry, 660 South Euclid Avenue, Campus Box: 8134, St. Louis, MO 63110. Or visit www.wustl.edu.

To contact Dr. Duman, please write to: Dr. Ronald Duman, Professor of Psychiatry and Pharmacology, 34 Park Street, Yale University School of Medicine, New Haven, CT 06519. Or visit www.yale.edu.

Then, commentator John Hockenberry muses on the discovery of neurogenesis - the process we've been discussing today, in which new cells, including new neurons, are born in the adult human hippocampus. He originally recorded this piece for The Infinite Mind show "The Decade of The Brain."

Finally, Dr. Kramer concludes the show with an essay summing up the importance of the findings discussed during the hour. These results suggest theories about what depression might be altogether. Perhaps depression is based in a special vulnerability to stress, or in early trauma that leaves the brain especially fragile in the face of further stress later in life. Depression may be a disorder of resilience, at two levels, psychologically and anatomically. And repeated episodes of depression may make it more difficult for people to recover from future stresses. He says, "Depression clearly is a disease -- a chronic, progressive one best approached with the public health mechanisms we apply to conditions like high blood pressure and arteriosclerosis- increased public awareness, early identification, early treatment, ongoing treatment, and extended follow-up."

For more information about depression, contact:

National Mental Health Association, 1021 Prince Street Alexandria, VA 22314-2971. Phone:1-800-969-NMHA [6642]; TTY: 800-433-5959

National Alliance for the Mentally Ill, Colonial Place Three, 2107 Wilson Blvd., Suite 300, Arlington, VA 2201. Phone: 703-524-7600; NAMI HelpLine: 1-800-950-NAMI [6264]

National Institute of Mental Health, NIMH Public Inquiries, 6001 Executive Boulevard, Rm. 8184, MSC 9663, Bethesda, MD 20892-9663. Phone: 301-443-4513; TTY: 301-443-8431

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