Written back in 2006:

A NY Times article on a gene related to ‘resilience’ inspired me to do some research on it.  The gene is 5-HTT and it encodes a protein that sits in the cell membrane and its function is to  ‘re-uptake’ serotonin.  There are two ‘versions’ (alleles) of the gene: a long and short.  The part that encodes the structure of the gene is the same in both.  The ‘promoter’ region is longer is the ‘long’ form, and so the long form is expressed more.  In other words, those with one long or two long have more 5-HTT proteins re-uptaking serotonin than those with short.

Now, if you’re familiar with anti-depressant drugs and haven’t read the article (which I’ll link to later), you may assume that those with longer forms might have a tendency to be more depression, because one of the main kinds of antidepressant drugs suppresses the re-uptake of serotonin (Selective serotonin reuptake inhibitors: SSRI’s).  In fact, the opposite is rather drastically true, though only one source I found mentions this contradiction.  Those with LL are much less likely to be depressed after a tragic event than those with LS/SL and they’re less likely than those with SS.

Something else to consider is that serotonin and 5-HTT are active elsewhere in the body, not just in the brain, and those with the rare and possibly deadly disease Primary  pulmonary hypertension (PPH, a lung disease) almost all have LL!   And no article I found draws this connection, so when the drug companies start rolling out drugs to make up for having one or two short versions…watch your lungs.

It’s rather depressing to me that in an hour of google research I’ve caught (I think) 2 misstatements (in press reports, but still) and connected 3 things related to this gene that no other article I found did (I did some cursory PubMed searches too, not just news articles).  The task at hand–understanding the complex interaction of various hormones and cells and genes and environment–is so complex and broad, and yet the current social organization of science puts shackles on the first baby steps. 

(Another connection would be the research presented by neuroscientist Elkhonon Goldberg in the Wisdom Paradox that connects curiosity at least partly to a hormone connected to serotonin, which leads me to think that LL expression may lead to less relative curiosity.  Given that and the link to lung disease and SIDS, the S version may be more evolutionary advantageous if one doesn’t live in a chronicly stressful environmental as we do.)

I think a rather obvious mechanism is that having more ‘re-uptake’ of serotonin leads to more efficient processing of it (the cell that reuptakes it can reuse it and the signal it’s sending is probably more precisely sent–it’s not as if more and more and more is better) leading to someone going through a stressful event to be better able to deal with it (as well as already being used to lower levels of serotonin perhaps), but someone with less reuptake would have a more precarious processing of serotonin that a stressful event could throw out of wack, leading to, among other things and through various mechanisms, too low levels of serotonin, with some of the resultant symptoms partially rectified–apparently ironically–by further inhibiting the reuptake of serotonin.  Remember: those with the short version are only more prone to depression depending upon the impact of stressful events–they are not ’sadder’ by default.  (This understanding would imply that while SSRI’s ease some symptoms, the underlying hormonal problem(s) still exists and are probably having other effects.)

Inspired by NY Times article on ‘resilience’.

http://www.nytimes.com/2006/04/30/magazine/30abuse.html

[Sidenote: The article says "It seems that only under dire circumstances — abuse, the strife of war, chronic stress — is the gene triggered [this isn't true at all, b/c the gene is being 'trigged'/expressed just as much as before].”  Given that this gene is being ‘triggered’ in higher and higher numbers in the US and abroad, one is left to ask–since the NY Times apparently didn’t think it fit to print–what kind of world we live in that ‘dire circumstances’ are becoming more and more common.]