Wednesday, 30 May 2012

Introducing "therapy genetics" - genes can predict whether therapy will help

Psychotherapy, like other forms of treatment, doesn't work for everyone and there would be huge advantages to knowing in advance who's likely to benefit. In the case of drugs, there's a thriving research field - pharmacogenetics - looking at whether a person's genetic profile can predict their chances of responding to treatment. Can the same approach be applied to therapy? A team of researchers at the Institute of Psychiatry in London believes so.

In one of the first papers published on "therapy genetics", Kathryn Lester and her colleagues, including Thalia Eley, took swabs from hundreds of white children with anxiety, aged 6 to 13. The researchers were specifically interested in the genes the children had that code for Nerve Growth Factor (NGF) and Brain Derived-Neurotrophic Factor (BDNF) - proteins involved in the survival and development of neurons. The children, some based in the UK and some in Australia, then underwent a CBT programme designed for helping anxious children. The key question was whether the children's genetic profile would be associated with how well they responded to the treatment.

There were no genetic associations with the children's immediate response to the treatment. However, at follow up (assessed at 3, 6 or 12 months), the children's particular NGF genotype was related to their therapeutic responsiveness. We each have two copies of the NGF gene, rs6330, which can come in two versions, known as the T allele or the C allele. Lester and her team found that among children with two copies of the T allele version, 76.7 per cent were free of their primary anxiety diagnosis at follow up, compared with 63.5 per cent of children with one C version and one T version, and just 53.2 per cent of children with two copies of the C allele. These associations held, even after controlling for other clinically relevant factors such as age, gender and geographical location.

Why should the children's particular form of NGF gene affect the way they respond to CBT? Definite answers will only come from more research, but Lester and her colleagues argued that the finding makes sense based on what we already know about NGF being involved in the growth of new neurons and in changing connections between existing neurones - known as "neuroplastic changes" in the scientific jargon. "Significant learning experiences of the kind undertaken during CBT may very well be underpinned by neuroplastic modifications in brain activity and function," they said.

This new result complements another recent paper published by the same research group, in which anxious children responded more successfully to CBT if they had a particular version of a gene involved in the activity of the neurotransmitter serotonin. Again, the association was found at follow-up rather than immediately after therapy.

Lester and her team said they believed the association they documented in this new research is "clinically meaningful", but that "clinically significant prediction by genetic markers is likely to be best achieved by combining multiple genetic markers (perhaps in combination with clinical predictors) into predictive indices or algorithms."

The research has some shortcomings. For example, without a no-treatment control group of anxious children, it's not possible to say for sure that NGF genotype is specifically associated with therapeutic responsiveness rather than an advantageous tendency to recover regardless of treatment. "These findings should be considered preliminary," the researchers said.


Lester, K., Hudson, J., Tropeano, M., Creswell, C., Collier, D., Farmer, A., Lyneham, H., Rapee, R., and Eley, T. (2012). Neurotrophic gene polymorphisms and response to psychological therapy. Translational Psychiatry, 2 (5) DOI: 10.1038/tp.2012.33

Post written by Christian Jarrett for the BPS Research Digest.


Anonymous said...

Was there any interaction with gender?

Disgruntled PhD said...

Please note the most important part of the paper:

Stringently correcting for all primary and secondary analyses presented on the three markers described here and in our previous paper with the 5-HTTLPR would require a Bonferroni adjusted P value of 0.002. None of the analyses reported here would survive this correction. However, we consider this to be very conservative given that the vast majority of analyses performed for each marker do not represent independent tests.

So essentially, given only the analyses reported (which were almost certainly a subset of the analyses done), if strict multiple comparison corrections are applied, then the results are not significant. Note that the sample size was 374, so these effects (if they actually replicate) are very, very small.

David said...

Hmmmm... yes, definitely "These findings should be considered preliminary" is the order of the day with this one!

Having worked for years in "therapy", as much as I could use both nature and nurture principles to make assumptions (which at best would be a "reasonable indication", but no more) I tend to get a better "feel" by asking intuitively; "is this person at thresh-hold?" and "do they really want to experience change through the therapy?". If the answer is yes to those two questions, they are going to respond well. If the answer is no... well, genetics or not, it's fair to say they are not going to respond as well.

I'm not sure this research has told us anything noteworthy... yet.


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