Genetic Vulnerability to Depression: A Blessing and a Curse?

Research has previously identified certain genes that may play a role in the development of depression and anxiety.

Specifically, individuals carrying the short variant of the serotonin transporter (5-HTT) gene have been found to be more susceptible to depression and anxiety. But, they are only more susceptible if they have experienced adverse life events.

Simply put, people who have experienced recent stressful events or were maltreated during childhood, are more likely to develop depression and anxiety if they possess this version of the gene. What’s more, is that individuals carrying the other version of the 5-HTT gene - the long variant - have been found to be at no greater risk for psychiatric problems following adverse experiences than people not exposed to stressful events.

All of this so far has lead to the short variant of 5-HTT having been labelled as a “vulnerability” or “risk” gene in the scientific community. In the media at large, 5-HTT has been called the “depression gene.”

A recent study conducted at the University of Münster in Germany may indicate otherwise, however. The findings suggest that instead of being a vulnerability gene, the short variant of 5-HTT may actually be a “sensitivity to the environment” gene.

In particular, possessing the short variant of 5-HTT not only seems to increase vulnerability to adverse experiences, but may also increase the likelihood that a person will benefit from positive experiences.                                     

Researchers tested out this hypothesis using male mice that had been genetically modified, so that their 5-HTT gene activity closely resembled that of humans carrying the short variant of it. They were then either provided with the beneficial experience of living with a female mate, or were housed alone (neutral experience). Mice that were not genetically modified, and more closely resembled humans with the long variant of the 5-HTT gene, were also provided with one of the two experiences.

Next, researchers tested the anxiety-like and exploratory behaviour of all the mice using behavioural tests. For example, in one of the tests used - the open field test - the mouse was placed in an unfamiliar enclosed arena for 5 minutes, while a researcher recorded what it did.

Given that mice genetically modified to resemble the short 5-HTT variant have been previously shown to exhibit increased anxiety-like and decreased exploratory behaviour following adverse experiences, it was predicted that they would display the opposite profile after positive experiences. Indeed, this is what the researchers found. 

Genetically modified mice who cohabited with a female showed reduced anxiety-like behaviours and increased exploratory behaviours. In comparison, the behaviour of mice who were not genetically modified did not differ based on whether or not they received this beneficial experience.

In other words, whether or not the mice benefited from the positive experience was dependent on whether their 5-HTT gene activity resembled that of humans with the short variant or the long variant.

All of this goes to support the idea that possessing the short version of 5-HTT may not be an entirely bad thing after all. Although research indicates that it places people at higher risk for depression and anxiety following adverse or stressful experiences, it may also bestow them with greater potential to benefit from positive ones. For better or for worse, some people may be more sensitive to their environment on the basis of their genes.

This may have important implications for the treatment of depression and anxiety. Because individuals with the short 5-HTT variant seem to be more susceptible to environmental influences, both good and bad, they may respond better to psychotherapy than people with the long variant. A recent study of low-income mothers suffering from depression indicates that this may indeed be the case.

In any case, it seems that for some their genetic makeup may be both a blessing and a curse. The same gene that contributes to suffering can also be of great advantage, all depending on the cards you are dealt.

-Kathryn Pierce

Reference

Kästner, N., Richter, S. H., Lesch, K., Schreiber, R. S., Kaiser, S., & Sachser, N. (2015). Benefits of a “vulnerability gene”? A study in serotonin transporter knockout mice. Behavioural Brain Research, 283, 116-120.