I Scream, You Scream, We All Scream for Gene Screens!

Will quickie genetic tests for suicide genes make us healthier and happier?


A study reporting the discovery of two genes linked with thoughts of suicide in patients on antidepressants was released yesterday in The American Journal of Psychiatry. The same day, a private company began selling fast, accurate cheek swab tests to identify the genes.

This might sound like great news—seemingly abstruse scientific breakthroughs helping sick people almost instantly. But this first step toward truly personalized medicine isn't going down easy in some quarters: "In my opinion, the results of the study would not be a sound basis for a medical test to decide what medication to give patients," said Dr. Douglas Levinson of Stanford's Program on the Genetics of Brain Function.

The test, called Mark-C, identifies the two risky genes (and two others to be discussed in an upcoming study). It allows patients and potential patients to find out if they are at higher risk for thoughts about suicide when they begin a regimen of Celexa, an antidepressant taken by 8 million Americans, and 30 million people worldwide.

The study, which was part of a large-scale project on depression, isolated a group of adults taking Celexa who reported thoughts of suicide in the course of their treatment. When scientists looked for shared genetic quirks in that group they found notable variants of two genes, GRIK2 and GRIA3, which control how the brain processes glutamate, an amino acid that facilitates communication between neurons in the brain.

Patients with those variations had more than 10-fold risk of suicidal thoughts compared with people without the targeted genes. Fully 36 percent of the patients who had both gene variations reported suicidal thoughts. 59 percent of the patients who had suicidal thoughts had at least one of the gene variants.

What all these numbers mean is that the test is good, but not perfect. Many people who have the genes don't have thoughts of suicide when on Celexa, and many people who have thoughts of suicide don't have the genes.

Some people, like the doctor quoted above, are worried that the public can't be trusted to understand the limitations of such tests, or comprehend of the state of the academic research.

Dr. Thomas Insel, director of the National Institute of Mental Health (NIMH), which helped finance the study, said the test "is not yet ready for prime time" for those reasons. NeuroMark paid the NIMH an undisclosed amount in August for the right to license a test for the genes.

But making the test widely available is very unlikely to do any harm, and may do a great deal of good. There are so many antidepression drugs on the market that the test is unlikely to dissuade anyone from getting treatment. Instead, it will encourage those with the genes to try drugs from a different family, increasing the chance that they'll get a drug that works for them sooner.

The test was rushed into general release, according to NeuroMark, partly in response to troubling statistics released last month by the Centers for Disease Control (CDC) showing a 8 percent rise in teen suicides in 2004. That was the year the FDA issued warnings about a possible link between teen antidepressant use and suicidal thoughts. The result was a massive nationwide scare, and it is thought that many parents took their teenagers off antidepressants, or decided not to begin treatment, perhaps causing an uptick in suicides.

The CDC breakdown of the data shows that the situation is even more serious for certain demographic groups: "The largest percentage increase in rates from 2003 to 2004 was among females aged 10-14 (75.9 percent), followed by females aged 15-19 years (32.3 percent) and males aged 15-19 years (9 percent)," according to the CDC.

While the link between thoughts of suicide and actual suicide attempts is tenuous, Kim Bechthold, CEO of NeuroMark, has said "We hope to save lives."

Even if those suicides couldn't have been prevented, many parents would be grateful to know if they are putting their kid at an increased risk while trying to help them with severe depression. This test won't answer that question completely, but it's a step in the right direction.

Announcing the release of the test, NeuroMark said, "We feel a sense of responsibility, given the current climate, to provide the test to physicians immediately so that they may identify patients who would benefit from closer monitoring or even a change in therapy. It is our hope that this early test will encourage more people to consider antidepressant drug treatment who would benefit from it."

The test costs a little under $500, and is not covered by insurance. This type of test does not require FDA approval, though it has been released in a manner that conforms to the Clinical Laboratory Improvement Amendments of 1988, and the company is seeking voluntary FDA approval for a version to be released next year.

So, is this the first step down a bold path to personalized medicine, or just a rush to exploit the national fear and uncertainty about side effects of antidepressants?

It's a little bit of both, and that's a good thing.

NeuroMark is aware the such a fast release is unusual—the study has yet to be replicated—and it is inviting doctors and patients to contribute to a database of self-described outcomes to extend the testing period for efficacy even though it is making the test available right away. Participants' identities will be protected, and participating doctors and patients will have access to new data as it becomes available. This is the first nationwide post-release data gathering operation of its kind.

At the same time, the identification of these genetic markers, and the quick transition into available medical technology is encouraging. Earlier this summer, The New York Times ran an article heralding the arrival of personalized medication for depression, which seems to be coming to pass even sooner than anticipated, in this small area, at least.

"We think this test represents the leading edge of personalized medicine," CEO Kim Bechthold. And she's right. Prescriptions based on the results of a cheek swab for suspect genes does sound awfully futuristic. Companies rushing to market with tests for the kinds of conditions and circumstande that make headlines will be a regular feature of the landscape.

People are bound to make medical decisions based on what they read in the paper more and more often in the future. And sometimes they'll make the wrong decisions, as the data suggest many parents did in the wake of the scare about teens and antidepressants in 2004. "Ripped from the headlines" marketing for medical tests may make some doctors uncomfortable, but for patients trying to make right decision with limited information, a speedy turnaround from lab to pharmacy good news.

Katherine Mangu-Ward is an associate editor of reason.

NEXT: No Hugging, No Learning

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  1. I think the test should be available, even though people wouldn’t know how to interprete it. Many people have difficulty understanding degrees of risk. They just lump things into safe vs deadly. That’s why they won’t distinguish between smokeless tobacco, pipe tobacco, and cigarettes. They also expect 100% certainty from scientific tests while this test just gives degrees of maybe. People who have trouble with these concepts aren’t ready to use the genetic tests. However, the solution is better statistics education, not a ban on the test.

  2. Some people, like the doctor quoted above, are worried that the public can’t be trusted to understand the limitations of such tests, or comprehend of the state of the academic research.

    This seems to mischaracterize the position of Douglas Levinson, the doctor who was quoted. He said, “Depression causes suicidal feelings. Whether there are additional people who got them because of the treatment rather than the depression they are experiencing has not been easy to establish.”

    Levinson described his own opinion about the usefulness of the test, concluding that it is not presently a clinically useful tool. So far as I can tell, he didn’t discuss the likelihood that the public would misunderstand the results.

  3. …and my do a great deal of good. There are so many antipepression drugs…

    Spellcheck, Katherine.

  4. Obviously, BakedPenguin has never known the trauma and heartbreak of seeing a loved one suffer from pepression.

  5. Suicide Kings?
    Suicide Girls?
    Suicidal Tendencies?
    Suicide Machines?

  6. These genes could be correlated to something else, such as a predisposition to get medical help for mental illness.

    They aren’t doing an epidemiological study of the whole population, identifying members with suicidal thoughts and running correlations on their gene sequences. These folks are self-selected as seeking help for depression, removing the assumption of independence, right?

  7. it’s a little more complex than “correlations”, but thank you for playing.

  8. I just watched a long speach about dialetic-behavioral therapy on the TV; the psychologist giving the speach made the point that we don’t really know anything, scientifically, about suicidal people because anyone deemed at risk of suicide is always eliminated from double-blind studies…

    She also said that it is a myth that depression alone causes suicide. According to her, only about 20%-30% of suicidal people are depressed. Something like 5%-10% have impulse control problems

  9. Wow, Dan T. says something good that makes me laugh out loud! And possibly even wins the thread.

    Just for that, I’m calling off the assassins.

  10. they can have my suicide genes when they pry them out of my cold, dead dna.
    Also, the most recent research indicates suicide genes and erection capability are intimately connected.

  11. My God, a suicide gene might explain why otherwise intelligent people latch on to candidates like Ron Paul. A possible flaw in this hypothesis is the “otherwise intelligent” part, but it’s worth investigating. Could libertarians have a genetic prediposition to opt for political suicide?

  12. Sorry, predisposition.

  13. Come on, Stevo, don’t act like it’s the first time!

  14. Pretty cool study, and I must say I’m pleased they narrowed their target gene population down to 68 from the 10,000+ you often see in this sort of work. This actually makes it probable the results are valid. Add to this that I’m actually working on GRIK2 and my results tend to lend support what they observed here and I think they might actually be on to something.

    All this work on glutamate in depression may be transformative, as most present treatments (including citalopram, the drug in this study)focus on serotonin or noradrenalin, and seem to take weeks to months to have an effect. On the other hand, ketamine, which is an antagonist at the NMDA subclass of glutamate receptors, seems to act almost immediately and have lasting effects from a single small dose.

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