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Dr. Bob is Robert Hsiung, MD,
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Posted by daorlando on December 4, 2006, at 9:28:28
http://www.bookofjoe.com/2005/05/behindthemedspe_5.html
Dr. Jonathan Roiser and his colleagues at Cambridge University this past March published the results of their work on the relationship between Ecstasy use and subsequent depression.It's long been known that there is a link, but beyond that not much could be stated with any certainty — until now.
Long version short: if a person has the short version of the serotonin–transporter protein (it comes in "long" and "short" versions) then they are significantly more likely to become depressed after using Ecstasy.
The two versions of the protein are produced by two versions of the serotonin–transporter gene, likewise known as "long" and "short."
Since everyone has two transporter genes, one inherited from each parent, a brain may have only long transporters, only short ones, or a mixture of the two.
Here's an excellent story from the March 12, 2005 Economist about the study.
The Agony and the Ecstasy
The link between Ecstasy, depression and geneticsOne of the most fashionable fields of medical science these days is pharmacogenomics.
This is the study of how people with different genetic make-ups respond differently to particular drugs.
The hope is that it will lead to high-precision prescription, with fewer side effects and better outcomes.
But what is sauce for the medical goose, is sauce for the recreational gander.
"Street" pharmaceuticals, too, might be expected to have pharmacogenomic interactions.
And so it turns out.
In a study carried out on users of Ecstasy (MDMA as it is known to doctors, and "E" to its consumers), Jonathan Roiser and his colleagues at Cambridge University have shown that someone's risk of developing long-term depression as a result of taking Ecstasy depends critically on his genes.
Their results are published this month in the American Journal of Psychiatry.
Ecstasy works its magic by affecting the concentration in the brain of a substance called serotonin.
This molecule is a neurotransmitter (a chemical messenger that carries signals from one nerve cell to another) that modulates mood and emotion.
Once it has done its job, it is sucked back into the cell that made it by a protein called a serotonin transporter.
This process both modulates the signal and conserves supplies of the chemical.
Ecstasy works by disabling the transporter protein, and at the same time opening the floodgates so that all the brain's serotonin is released in one glorious gush.
Serotonin transporters, however, come in two varieties—the result of there being two versions of the gene that encodes them.
These varieties are known as "long" and "short", and since everyone has two serotonin-transporter genes, one inherited from each parent, a brain may have only long transporters, only short ones, or a mixture of the two.
Previous research has shown that having even one copy of the short gene makes a person more likely to suffer depression after a stressful event, such as losing a job.
It is also known that those with the short version respond less well to a class of antidepressants called selective serotonin reuptake inhibitors (SSRIs), the best known of which is Prozac.
It was in this context that Dr Roiser wondered if Ecstasy users who had inherited the short form were at heightened risk of depression, too.
Dr Roiser and his colleagues invited 66 heavy users—people who had taken the drug at least 30 times—to participate in their study.
These volunteers agreed to abstain from their pleasure in the three weeks prior to the tests being carried out, so that the effect of the drug itself, or its immediate aftermath, were not accidentally measured.
For comparison, they asked 28 people who had never taken illegal drugs to join in and, for good measure, they had 30 regular cannabis users as well.
The team employed two well-known indicators of depression to evaluate their subjects.
One was a standard questionnaire, known as the Beck Depression Inventory, that taps into depressive thinking.
The other was the Affective Go/No-Go test, which is done on a computer. This measures how much influence happy or sad words have on how quickly or accurately a person performs a task.
Typically, healthy people respond faster following happy words, while depressed people respond faster after sad words.
The researchers also took blood samples to determine what kinds of serotonin-transporter genes their volunteers had inherited.
Using the depression inventory, the team found that people who employ Ecstasy regularly, and who have two short versions of the gene, are significantly more likely to suffer from mild or serious depression than the others.
Importantly, the double-shorted folks who did not use Ecstasy were not more likely to have depression, and neither were double-shorted cannabis users.
The Go/No-Go task also indicated depression in Ecstasy users with short versions of the gene—and in this case, just one short gene was enough to confer increased risk.
Again, people with short genes who had not used the drug were unaffected, even if they used cannabis.
The researchers therefore think that those with the short variant are especially vulnerable to the effects of the drug.
Conversely, those who are long on serotonin transporters seem to be at no added risk of depression from their drug use.
That leads to two conclusions.
One is that prescribing SSRIs for Ecstasy-induced depression probably won't work, for pharmacogenomic reasons.
The second is that if Ecstasy were a legal drug, the knowledge Dr Roiser has revealed would surely lead to testing kits, so that users could check their vulnerability.
Perhaps it ought to anyway.
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My question: if SSRIs or 5htp won't work for Ecstasy-induced depression for folks with short genes, what will?
Posted by Sebastian on February 17, 2007, at 20:56:57
In reply to Depression after Ecstasy use genetically–linked, posted by daorlando on December 4, 2006, at 9:28:28
Ecstacy? For there depression?
This is the end of the thread.
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