For over twenty years, there’s been interest in the idea that changes in the serotonin transporter protein might be associated with depression in humans. The hypothesis makes some sense on the face of it, although the entire serotonin/depression connection is a lot more complicated than it’s thought to be in the popular imagination. There’s a polymorphic region (5-HTTLPR) in the gene that codes for the transporter, so it’s tempting to imagine that variations in the tendency towards depressive disorders might correlate with it.
I would not want to try to summarize the literature on this, but it is extensive (that Wikipedia article will give you some idea, as it takes you through the yes-there-is-no-there-isn’t cycle). This new paper, though, is trying to put the question to rest once and for all. Going back over 31 separate data sets, including unpublished ones and totaling over 38,000 patients, the consortium involved finds. . .no evidence for the hypothesis. Even the idea that the polymorphism might only show up as meaningful in life-stress situations takes a hit, since the new analysis suggests that this effect might be so modest and so conditional that it’s essentially of no practical use. This conclusion has been sneaking up on those in the field for some years now, with phrases like “It seems virtually certain that the links between 5-HTTLPR and depression are more complex than previously thought” appearing frequently.
An awful lot of time and effort has gone into this over the years, and it would appear that the entire thing has been a blind alley. In retrospect, it was a lot to hope for that variations in a single protein could be a linchpin for a complicated human central nervous system condition, and maybe that’s a lesson that everyone can take from this. Higher functions of the human brain, especially whatever it is we’re talking about when we use words like “personality” or “temperament”, are probably not going to break down to genes so simply, which will certainly come as a disappointment to people writing headlines for magazines and web sites.