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"Suicide linked to defective gene"

Posted by dj on January 28, 2000, at 16:34:58

Suicidal tendencies treatable, Ottawa scientists say: Discovery raises concerns genetic marker will be used to stigmatize people who have it

Brad Evenson
National Post

Dr. David Bakish, and Dr. Pavel Hrdina of the Royal Ottawa Hospital led the study that found a gene mutation that more than doubles the risk of suicidal behaviour. The discovery could lead to a "suicide test."

OTTAWA - Confirming a 2,000-year-old belief that self-destructiveness runs in families, scientists from the Royal Ottawa Hospital have found that a gene mutation leads to suicide.

The discovery may lead to a "suicide test" that would identify patients at risk and could also open a philosophical debate on how this dark fragment of personality will be used in an age when medical records are kept electronically and are difficult to keep confidential.

The researchers found a mutation in the gene encoding for the serotonin 5-HT2A receptor, a protein that transmits brain signals, which more than doubles the risk of suicidal behaviour in those who carry it.

"Individuals who carry the [mutation] are at higher risk when a situation that triggers their suicidal tendencies will occur," says neurobiologist Dr. Pavel Hrdina, who co-authored the landmark study.

The study looked at patients suffering from major depression, so its results do not apply to healthy people who may attempt suicide as a one-time "cry for help" or to gain attention. However, the researchers say it is possible the 5-HT2A receptor mutation may also be linked to the elevated risk of suicide among schizophrenics.

People have believed since Biblical times that mental illness and suicide are inherited.

When Margaux Hemingway committed suicide in 1996, it gained attention not only because she was the world's highest-paid model and the granddaughter of Ernest Hemingway, but because it marked four generations of suicide in the famous American family.

"Alcoholism and suicide seem to be something we Hemingways have inherited," she once said.

A diagnostic test for this trait would identify people in need of medical help, including gene therapy. Suicide is now the world's ninth leading cause of death and growing fast. Each year in Canada, there are 30,000 suicide attempts; on average, 4,000 succeed.

"Suicidal ideation is a treatable condition," says co-author Dr. David Bakish.

"This could help save lives."

However, this mutation could also prove to be a "Scarlet Letter" whose presence makes it impossible to buy life insurance, fly an airplane, or even hold a position of trust in society. The risk of unwanted exposure may be considerable.

"There are huge issues of privacy and discrimination here, and they just get ratcheted up because you're talking about psychiatric illness," says Dr. Kay Redfield Jamison, a professor of psychiatry at Johns Hopkins University in Baltimore, Maryland.

The discovery will be published on Feb. 7 in the American Journal of Medical Genetics. Along with Drs. Hrdina and Bakish, the researchers included molecular geneticist Dr. Lisheng Du, and Drs. Yvon Lapierre and Arun Ravindran.

In the study, the Ottawa researchers looked at blood samples from 120 patients with major depressive disorders, of whom 78 were suicidal and 42 were non-suicidal. They compared these with samples from 131 men and women with no mental illness.

An analysis of the DNA showed 41% of the suicidal patients had the 5-HT2A receptor mutation, compared with 24% of the non-suicidal patients and 18% of the healthy subjects.

"In biological terms, that's a tremendous difference," said Dr. Hrdina. He stressed the results would have to be replicated before they gain scientific acceptance.

Located on the long arm of chromosome 13, the mutation can be detected from a droplet of blood in almost any laboratory with advanced gene identification equipment.

The principal function of the 5-HT2A receptor is to transmit signals from serotonin, a brain chemical that puts the brakes on impulsive thoughts that may develop in the cerebral cortex. Over 50% of suicide attempts take place with less than five minutes of premeditation, so impulse is known to be a strong contributor.

It's believed the 5-HT2A receptor gene mutation may weaken the brain's ability to control the impulse to commit suicide. There may also be more mutations to genes controlling serotonin levels that may increase the risk of suicide.

However, the presence of this mutation does not mean suicide is inevitable.

In her new book on suicide, Night Falls Fast, Dr. Jamison points out: "It simply makes it more likely that given enough cumulative stress or a devastating, acute one, suicide may be an option more readily summoned."

She continues: "A genetic vulnerability for heart disease, cancer, or asthma, for example ... does not ensure that illness will occur."

Dr. Hrdina said significantly more males in the study had the mutation than females. While it's premature to say what this result means, four times as many males die of suicide as females -- although women attempt to kill themselves in numbers roughly equal to men.

A genetic variability might also explain why suicide rates vary strongly between populations with different ethnic origins. For example, the annual suicide rate in Finland (for males) is 43 per 100,000 people, one of the highest rates in the world.

But the rate for neighbouring Norway is only 21 per 100,000, less than half.

"It may be interesting to look into the distribution of the [mutation] in these countries," said Dr. Hrdina.


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