The long and the short of it: how gene length could influence our emotions

Prof. Elaine Fox

What causes mental illnesses such as anxiety disorder or depression? Are some people more likely to develop these conditions than others? What is the best way to treat them? These are just some of the challenging questions that Professor Elaine Fox, a psychologist at the University of Essex, is trying to answer. She and her colleagues have recently found that a variation in the gene that encodes a particular protein could make some people more sensitive to their emotional environment – and more susceptible to anxiety disorders – than others. I spoke to Professor Fox to find out more.

Which protein have you been studying?

We’ve been looking at the serotonin transporter, a protein that ‘recycles’ serotonin [a neurotransmitter] during nerve signalling. When a nerve signal is passed from one neuron [nerve cell] to the next, serotonin released by the first neuron carries the signal across the gap to the second neuron. Afterwards, serotonin transporters remove serotonin from the gap and return it to the initial neuron, ready to be released again when another nerve signal is transmitted.

Why were you interested in it?

We’ve known for a while that the gene that contains the instructions for making the serotonin transporter seems to play a role in increasing the risk of a person being emotionally vulnerable, particularly in relation to depression and anxiety.

This gene varies across the population. Some people have short versions that result in them having fewer copies of the serotonin transporter, and therefore higher concentrations of serotonin in the gaps between neurons. Others have long versions of the gene that lead to more copies of the serotonin transporter and lower serotonin levels.

About a year ago Arne Öhman, and his group from the Karolinska Institute in Sweden, published a paper that showed that people with short versions of the serotonin transporter gene learnt to fear [by exposure to a “highly annoying but not painful” electric shock] much more quickly than people with long versions.¹ Their findings suggested that these people have brains that are much more reactive to threat.

I thought it would be really interesting to look at this link between the serotonin transporter gene and how the brain learns in the context of the attention bias modification (ABM) procedures that I was already using.

What are attention bias modification (ABM) procedures?

They are techniques that can be used to change the amount of attention a person pays to something, known as an attention bias. ABM training typically involves using a computerised training programme to alter a participant’s attention bias.

It’s normal for healthy people to have low levels of ‘trace’ attention bias, which may focus their attention slightly more towards either positive information [if they have a positive trace attention bias] or negative information [if they have a negative trace attention bias].

People with anxiety disorders have a very strong bias in their attention towards threats [a negative attention bias that is much larger than the trace levels found in healthy people]. The interesting question is: do people with anxiety disorders have a strong negative attention bias because of their anxiety, which tunes them into things that are threatening, or are these biases part of the reason why people have developed anxiety in the first place? The evidence now indicates that the biases can indeed cause anxiety problems to develop.

We want to find out whether ABM techniques can be used as a treatment to reduce negative attention biases in patients with anxiety disorder, and therefore reduce their emotional vulnerability. It may be that they won’t be used as a stand-alone intervention, but might actually be very powerful if combined with other techniques, like cognitive behavioural therapy [a talking therapy] or drug therapy.

What did you do?

We combined ABM training with genetic testing for the first time, to investigate the relationship between the serotonin transporter gene and how quickly people can “learn” to develop a bias in attention².

Our experiment involved testing two groups, each of 57 healthy people. We used computer-based tasks to test whether the volunteers had an initial trace attention bias towards either positive or negative images, and then gave them ABM training to induce a positive bias in one group and a negative bias in the other. We then re-tested participants to see if their initial attention biases had changed, and whether their performance varied according to which version of the serotonin transporter gene they had. Both groups contained some people with short versions of the serotonin transporter gene and others with long versions.

Attention bias testing involved briefly presenting two images at the same time, side-by-side on a computer screen. One image was highly positive [e.g. a smiling baby] and the other was highly negative [e.g. a snarling dog]. Both images disappeared after half a second and one of them was replaced with a symbol. We measured how quickly a participant was able to identify the symbol, and used this to calculate their attention bias. For example, if someone was more tuned into the positive, they were slightly faster at finding the symbol when it appeared in the location where the positive item had been, compared to when it appeared where the negative item had been.

Each participant’s response time was measured 128 times, in which there was equal probability of the symbol replacing either the positive or negative image.

ABM training was conducted in almost the same way as attention bias testing. Over hundreds of trials, people saw pairs of images flash up on the screen, followed by a symbol. The difference between this and the testing was that the symbol always replaced the positive image during positive attention bias training, and always replaced the negative image during negative training.

We were orientating people’s attention system towards either positive or negative information [depending on which training group they were in], even though they weren’t really aware that the symbol was always appearing behind the same type of image.

What did you find out?

People with a short serotonin transporter gene developed stronger biases over an hour’s training session than those with long versions of the gene. The unexpected finding was that this was true for both negative and positive information. In other words, people with short forms of this gene were more sensitive to the emotional significance of their surroundings, irrespective of whether that environment was positive or negative. This means that they are likely to be far more reactive to very negative situations, such as a car crash, putting them at higher risk of developing emotional vulnerability.

On the other hand, when they experience something very positive such as a supportive relationship, they may be able to benefit from it far more than someone with a long serotonin transporter gene would. This supports the idea of short serotonin transporter genes as ‘adaptability’, rather than ‘vulnerability’ genes, or what you might call a “make you or break you gene”.

In healthy people, a trace attention bias is not likely to have a dramatic effect on a day-to-day basis. The idea is that these biases are not particularly damaging in themselves, but over time they really do start changing brain states. If you imagine someone with a small negative attention bias who experiences negative events 8 or 9 times every day, over a month, a year, or many years, that could really build up to produce a different brain state and a different world view.

We’re arguing that the kind of biases that people have in their attention plays a causal role in the development of emotional vulnerability. In other words, if people are tuning into the more negative aspects of their surroundings, it can make then more reactive to stress.

What are you planning to do next?

I’m hoping to follow up this work. The idea is to look in more detail at how patients with different versions of this gene respond to various therapies for anxiety disorder and depression, such as ABM procedures, cognitive behavioural therapy and drug therapy. It would be really nice to see whether the type of serotonin transporter gene that a patient has makes a difference to how beneficial those treatments are.

That would be the first step towards a much more ‘personalised medicine’ approach, in which genetic information about a person with anxiety or depression could help with decisions about how to treat them. I also think that there is a lot of work to be done to understand the basic science behind cognitive biases and how they impact on emotional disorders.

This study was funded by a University of Essex Research Promotion Fund Grant and a Wellcome Trust Project Grant.

References

• Lonsdorf TB, Weike AI, Nikamo P, Schalling M, Hamm AO, & Ohman A (2009). Genetic gating of human fear learning and extinction: possible implications for gene-environment interaction in anxiety disorder. Psychological science, 20 (2), 198-206 PMID: 19175757
• Fox, E., Zougkou, K., Ridgewell, A., & Garner, K. (2011). The Serotonin Transporter Gene Alters Sensitivity to Attention Bias Modification: Evidence for a Plasticity Gene Biological Psychiatry, 70 (11), 1049-1054 DOI: 10.1016/j.biopsych.2011.07.004