Testing for the short serotonin transporter allele
Summary: If you’ve had a rough childhood and long struggle with depression, would it help to know that you had two short serotonin transporter genes? For some people it might. But it might make others think they shouldn’t have children, and that could be a great misfortune.
That’s because the short version of the gene is not a “risk” gene. It’s a “plasticity” gene. It helps the carrier adjust to the environment in which she or he is going to grow up. The process starts even before birth. Even before conception, in her parents’ experience of the world (not just her parents’ gene lengths).
So even though you can buy the test now, it’s almost certainly too early to know. Because the people who are studying these gene effects don’t really understand what their significance is. And because even if we knew a great deal about one gene’s effects, we have almost no idea about how that gene interacts with other genes — except that we know those interactions are extremely complex.
One thing is clear: “risk gene” is an oversimplification. Don’t be misled.
While the summary above was written in 2014, the rest of this page is my old stuff from the last decade. It’s not wrong but it’s old. This page is on my short list for a major re-write because there is fantastic new stuff to report. Unless you are on the verge of ordering some genetic testing, skip the rest of this and move on to Chapter 6.
When I show this “shorts and longs” story to patients, their reaction is often “where can I get tested?”. But we’re very early in this game. This may not be such a great idea. Let’s look briefly at some of the pros and cons of testing the length of your serotonin transporter alleles.
In Favor of Testing
Reason #1: I want to know.
My patients are clearly voting in favor of testing, at least judging by their initial reactions. They seem pretty certain that they’ll be “two shorts” people. They seem to be saying: if I knew this, I’d have a good solid reason for how I feel, finally.”
Why might that help? Perhaps they want an explanation (even if they never voiced it) for the people who think “you shouldn’t be so weak; you shouldn’t be so sensitive; you ought to just pull yourself together and get on with life”, and so forth. Do people with “two longs”, who seem to be so resistant to stress effects on mood, really look at others who have struggled and somehow send such a message? Isn’t that a common attitude? Doesn’t the general message from our society, here in the U.S., sounds like that? For example, in the U.S., the idea of “being on welfare” is a very negative idea. Politicians know our populace looks down upon the general idea of “welfare” — as though in most cases needing it was some kind of a choice people made, and could have made differently. (I find it encouraging to know that the attitude in much of the European Union is nearly the opposite, as described in the recent book, The United States of Europe, by TR Reid).
So perhaps my patients are looking for a way to explain to the yellow people, the “two longs” types”, why they, the blue people, have been struggling. See? — I’m different than you are, I faced a bigger challenge, that’s why things keep turning out the way they do”. But I think even more important is the chance for an explanation for themselves. Ah, there, you see, now I know why it’s been so tough”.
Either way, these might be sufficient reasons to test, as long as the person is prepared for a “two longs” answer (or statistically much more likely, a “one long, one short” answer, which accounts for about 50% of the population). This may not be how we doctors were taught to use laboratory tests. But we often consider much more expensive tests such as MRI scans just to know what’s going on, not to guide treatment.
Reason #2: I’ve heard it can tell you which antidepressant will work best.
That’s what the lab which now offers it says, anyway. This is based almost entirely, as best I can tell, on a single studyMurphy — although that study had remarkable results, like this:
These graphs show the number of people who stopped the medication over the study period of 48 days — up to half of them, as you can see on the left: the gray bar tops out at 50%. As you can see, over time, more and more people have quit. On the left are results for paroxetine (generic for what we used to call Paxil in the U.S.), and on the right is mirtazapine (trade name Remeron, also available as a generic) . The gray tracing represents the people whose blood test showed they have “two shorts”. The black tracing is the “long/long” group; and the dark gray line in the middle is the “long/short” group.
According to this study’s results (and the lab that is offering the testing), if you knew in advance that you have two shorts, you’d definitely want to start with mirtazapine rather than paroxetine; and vice versa — long/longs should start with paroxetine. Too bad that already another study has found nearly the opposite results.Kim You may have seen similar contradictory results in the last chapter.
Although this is only a single study, I have to admit: if I had a lot of patients for whom I was trying to choose between these two particular antidepressants, I’d be curious about my patients’ long/short status; perhaps it would indeed help avoid some problems. BUT: a) that pair of medications is not a common choice; and b) mirtazapine is not a common option to consider because it causes weight gain, big time, in a lot of people, a lot more than the other antidepressants have the tendency to do. We don’t know if these results apply to any other antidepressants (there is a hint in two studies that the short/short combo’ is associated with more bipolar-like responses to antidepressants, but that has not been consistently shown enough, yet).
So, I think it’s too early to start actually using this test for this reason. It’s going to be interesting, though, now that there is indeed a lab which offers it (they don’t say what the cost is; does that mean “if you have to ask, you can’t afford it?” If I was an insurance company I’d be scrambling to block having to pay for this test, at least for now, until we know more about how to use the results to get better outcomes.
Here are three reasons that testing might not be such a great idea:
- It’s not how we’re taught to use tests.
- We don’t really know the full meaning of what we’re testing for.
- What might happen based on having this information?
1. Using Tests
First, there’s a simple argument, one taught in medical school. It goes like this: think about what you’re going to do if the test is positive (shows a disease present, for example). Think about what you’re going to do if the test is negative (shows the absence of that disease, for example). If your plan of action is the same in both cases, don’t order the test — because tests cost money, can carry risks for patients, and can through false results lead to yet more tests with yet more risks and costs,
Obviously the idea here is that tests are supposed to guide action. They are not ordered “just to know”. But we violate that rule all the time, we doctors — sometimes because we want to know, and sometimes because our patients do. There is clearly a psychological benefit, sometimes, in knowing why a symptom is occurring, even when knowing why won’t make the symptom go away. People talk about the odd relief they feel, sometimes, when given a bad diagnosis, just because now they have an explanation for something that had been worrying them.
The trick, in my view, is to be prepared for getting the answer you didn’t expect. What if you’re a “two longs” person? Might you be set back by this discovery, when you were hoping for an answer that would have helped you? Might there be a risk in getting set back, like that, which may even outweigh the potential value of being told “two shorts”?
2. What are we testing?
This whole story of “shorts and longs” is just now being brought to light by research teams like Klaus-Peter Lesch’s group in Germany. We don’t even really know what these results mean. The graphs in Chapter 1 here, by Dr. Caspi and colleagues, were published just over a year ago. Although these results are extremely strong statistically, and seem to paint a fairly clear picture (if they didn’t, this would not be such a compelling story), the picture is still a “work in progress”. We still don’t really understand what the long allele is doing so differently than the short allele. Perhaps we should know, before we start testing people. What if people start choosing not to have children if they have two shorts”, for fear of setting their children up for the kind of struggle they themselves may have had — and then we learn later than the short gene also predicts genius, or some other highly valuable resource to society? [Update 2014: that’s indeed what some of the most recent data are suggesting. Not genius, necessarily, but “better off than with two longs”, if growing up in a benign childhood environment].
3. Potential for misuse of the results
Some ethics specialists have recommended against this kind of genetic testing, concerned that it might actually increase stigmatization, rather than lower it.Morley For example, if testing serotonin transporter allele lengths became common,
might an insurance company try to use the results to deny you life insurance — or even health insurance? They already restrict coverage for “pre-existing conditions”, right? And they clearly feel like they can up any rule they want, about whom they cover and how (don’t get me started there…). So, do you want something on record now, before the rest of this story becomes clearer, including how such information might be used?
These are just some things to think about before going off looking for testing — as surely someone is going to offer this kind of thing over the internet in not too long.