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A Suicide Gene
Is there a genetic cause for suicide?
By Sharon Guynup

Featured Article.

The pattern seems so familiar: a business reversal, the breakup of a marriage, school failure, depression, a downward spiral leading eventually to suicide. The apparent links between failure, depression and suicide have become a cultural icon, appearing over and over in movies and books.

Ottawa-01/27/00 Dr. David Bakish (right), Head of Psychopharmacology Unit at the Institute of Mental Health Research at Royal Ottawa Hospital and Dr. Pavel Hrdina, Head of the Neuro-pharmocology Lab at the ROH hold an album of photos of the alleles of serotonin receptor gene.

But increasingly, researchers are becoming convinced of an entirely different cause of suicide: a chemical imbalance in the brain. A recent study reinforces this view, says David Bakish, a psychiatrist at the Royal Ottawa Hospital. Bakish studied patients who could not stop thinking about killing themselves and who had a family history of suicide. What he found surprised him. The patients' brain cells had changed in an apparent attempt to make up for a lower than normal amount of a common brain chemical. "That's when the light bulb went off," Bakish says, who thinks depression may not be the only cause of suicide. "Maybe it's a genetic trait." If this is true, the implications for the study and treatment of suicidal individuals are significant.

For some, suicide is a one-time cry for help, Bakish says. But others simply can't control suicidal fantasies, nor can they stop themselves from attempting to take their own lives. Bakish, along with other researchers of the hospital's Institute of Mental Health Research, found that these desperate acts may arise from a genetic mutation. The researchers published their results in a recent issue of the American Journal of Medical Genetics.

The discovery could lead to the development of genetic tests to identify those at risk. But it also poses questions about the ramifications of such testing. During their 10-year study investigating the causes of suicide, the Canadian team discovered a genetic variation that affects brain chemistry. They found that depressed individuals with a mutation in the gene encoding the serotonin 5-HT2A receptor are more than twice as likely to attempt suicide as those who suffered from depression but did not carry the mutation, says Pavel Hrdina, a neurobiologist at the Royal Ottawa Hospital and study co-author. Serotonin is a neurotransmitter that carries messages between brain cells and is thought to be involved in the regulation of emotion, among other functions. For some years, scientists have suspected that the genes regulating the serotonin system could be one of the culprits.

The finding adds support to a 2,000-year-old belief, dating back to Biblical times, that mental illness and self-destructiveness run in families. Epidemiological studies also back up this idea. For example, two countries that top the world's suicide rate list are Hungary and Finland, with 40 suicides per 100,000 people. Although the countries lie 1,600 kilometers apart, their people share a language group and, presumably, genes. The Finno-Ugric people lived together for thousands of years in the Ural Mountains of what is now Russia, then migrated to Finland and Hungary.

10 to 15 genes may act in concert to trigger suicide

The medical literature has documented many genetic links to suicide. One such study, published in the American Journal of Medical Genetics in 1985 examined the rate of suicide among the Amish population in southern Pennsylvania. Genealogical and medical records revealed that four families accounted for 73 percent of all suicides, but represented only 16 percent of the total Amish population.

"Genes are, of course, only part of the tangle of suicide, but their collision with psychological and environmental elements can prove…to be the difference between life and death," writes Kay Redfield Jamison, a psychiatrist at Johns Hopkins, in her book on suicide, Night Falls Fast.

When the Ottawa project began 10 years ago, researchers first analyzed the brains of Hungarians who had died at their own hands, specifically looking at serotonin receptors. They found that these brains had an overabundance of 5-HT2A receptors. This suggested improper absorption of serotonin. If cells are not getting enough serotonin, they build receptors in an attempt to soak up more.

This finding was later mirrored when the researchers tested 120 patients who suffered from persistent suicidal fantasies. Because blood platelets also carry serotonin receptors, Dr. Lisheng Du, the team's molecular geneticist, analyzed blood samples from the patients and from 131 control subjects with no history of mental illness or substance abuse.

"What we found was fascinating," said Bakish. "The patients had 40 percent more of these receptors than normal." Forty-one percent of the patients in the study carried the genetic mutation, compared with 18 percent of control subjects.

When these patients were treated with a variety of antidepressants, the only medications that alleviated their suicidal fantasies were drugs such as Prozac™, which belong to a family called selective serotonin reuptake inhibitors. These drugs prevent brain cells from overdoing the normal mop-up operation after they release serotonin. This was the true test. If, with treatment, the receptor numbers remained constant, the condition truly was genetic in origin. "The numbers didn't change," says Hrdina. But he cautioned that other laboratories must replicate the findings before the search for more finely tuned drug therapies can begin.

The identification of successful treatment could have far-reaching implications. In the United States, 13 out of every 100,000 people—about 30,000—kill themselves each year, and suicide has become the third leading cause of death for 15 to 24 year-olds. And the U.S. is not alone. In 1998, the World Health Organization ranked suicide as the twelfth leading cause of death worldwide—948,000 people died of self-destructive acts.

Hrdina and his team are currently studying suicidal fantasies among schizophrenics—and hope to look for this same biological marker in other populations as well, including alcoholics and drug abusers. As many as one in four schizophrenics commit suicide. Then the researchers will ask how interactions among several genes might come into play. Hrdina suspects that 10 to 15 genes may act in concert to trigger suicide.

A diagnostic test for this trait could identify patients at risk. And careful monitoring of these individuals could save lives. "You may carry this gene and it may never be expressed unless some big environmental factor comes along," said Bakish—such as a death in the family, divorce, loss of a job, or some other stressful catalyst.

However, as with other genetic tests, a test for the tendency to commit suicide carries with it a duty to be responsible—to "do no harm." As with all genetic tests, and other private medical information for that matter, the issue of discrimination by employers or insurers needs to be resolved. For now, Bakish hopes those with a family history of suicide and those with persistent fantasies of suicide will seek help. "Families have always swept suicides under the rug," says Bakish, who argues that having a biological marker really should de-stigmatize mental illness. "It's not a character flaw. It's something you're born with, like many other diseases."

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Du, L., Bakish, D., Lapierre, Y.D., Ravindran, A.V., & Hrdina, P.D. Association of polymorphism of serotonin 2A receptor gene with suicidal ideation in major depressive disorder. Am J Med Genet (Neuropsychiatr Genet) 96, 56-60 (February 7, 2000).

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