Probing the suicidal mind
Mon, July 12, 2004
by Mark Johnson, Milwaukee Journal Sentinel

MILWAUKEE - (KRT) - In large, ultracold freezers at the New York State Psychiatric Institute lie the brains of 200 people who committed suicide, and maybe some insight into why they did it.

Researchers examining the brains are only beginning what looks like a long journey into the deep recesses of the suicidal mind.

"We know some, and we don't know a lot," said Victoria Arango, a professor of neuroscience at Columbia University who has studied the brains with collaborator J. John Mann. After 15 years, she said, "there's still many questions remaining."

What she and Mann have found so far is that people who commit suicide have lower-than-normal levels of serotonin, a brain chemical known for its calming effect.

They believe this lack of serotonin affects the number of receptors for the chemical in the section of the brain just above the eyes, the orbital prefrontal cortex - birthplace of our impulses. Because suicide has been tied to impulsive behavior, this area of the brain is of keen interest to scientists.

But serotonin depletion is also found in people who aren't suicidal, just highly frustrated, discouraged or depressed.

This is one more riddle facing researchers as they hunt for factors that predispose a person to suicide, knowledge that could lead to treatments that keep suicidal urges in check.

Another riddle challenging scientists is the apparent difference between teenage suicides and adult suicides. Teenagers appear to be driven to suicide more often by impulsiveness and stress, rather than by psychiatric disorders such as depression, said G.N. Pandey, a professor in the department of psychiatry at the University of Illinois at Chicago.

"There is no one single suicidal personality," said Justin Draguns, a professor emeritus of psychology at Pennsylvania State University. "It is committed by a lot of very different people with a lot of very different motivations."

In 2002, more than 30,000 Americans killed themselves, making suicide the nation's 11th leading cause of death. Almost as many people died from suicide as from homicide and HIV combined, according to the Centers for Disease Control and Prevention.

Among children 5 to 14 years old, suicide is the fifth-leading cause of death; among 15- to 24-year-olds, it ranks third. Accidents, including traffic fatalities, are far and away the leading killer for both groups.

Progress has been made in our understanding of suicide. Studies indicate that stress is an important risk factor. Also, a relatively high percentage of suicides involve alcohol or losses (the loss of a job, or loss of a relationship), said Daniel Amen, medical director of Amen Clinics in California, a facility that uses a technique called brain SPECT imaging to evaluate blood flow and patterns of activity in the brain.

"Men who are batterers also have a much higher incidence," Amen said.

Suicide appears to run in families, too. A 2002 study in the Archives of General Psychiatry examined families with mood disorders and found that the children of people who attempted suicide were six times more likely than children of non-attempters to try killing themselves.

Research has also shown that suicide may be related to the loss or atrophy of brain cells and connective tissues. A study in the American Journal of Psychiatry even found a link between cigarette smoking and suicidal behavior; the reason may be that smoking hinders the work of serotonin in the brain.

Despite such advances, our understanding of the suicidal brain is still in its infancy.

"If you commit suicide in Milwaukee today, nobody will look at your brain," Amen said. "They'll talk to your mother. They'll look at your symptoms. But nobody will look at your brain. I think that's wrong."

The brains stored in the freezers in New York weigh about 2.5 to 3 pounds apiece; all were obtained with the permission of victims' families.

They are grayish, wrinkled lumps surrounded by membranes that can appear bloody. The freezers in which they're stored are set at minus 112 degrees Fahrenheit - far colder than the freezers in most American homes.

Arango and her colleagues remove the brain stem, and divide the remainder of the brain into the right and left hemispheres. They cut the right hemisphere into slabs, freeze them and recut them into slices just 20 thousandths of a millimeter - so thin they're transparent.

These ultra-thin slices are placed on glass slides for examination.

Arango and her colleagues have studied the deficit in serotonin. There are 14 different serotonin receptors, which appear to fill different functions: one is involved in aggression, another in anxiety.

Arango has determined that the serotonin deficit in suicide victims is not caused by a lack of cells making the chemical. Rather, something in the process appears to be going wrong.

Not all research on the suicidal brain has focused on serotonin.

A 2003 study published in the Archives of General Psychiatry found the brains of suicide victims contained lower-than-normal levels of one receptor and one especially important neurotrophin, a chemical involved in the survival of brain cells.

Yet another study published in the same journal in 2003 found abnormalities in the brains of suicide victims involving a protein that turns genes on and off.

As scientists learn the characteristics of the suicidal brain, they hope to tailor medications that will correct or compensate for the abnormalities.

"If we know the biologic abnormalities, we can come up with better target sites for the drug, which will be more effective," said Pandey at the University of Illinois-Chicago.

"It's a kind of continuous process. I don't think in the near future a perfect drug will come."