The Genetics of Trauma

One of the biggest promises of the Human Genome Project was that this newfound treasure trove of genetic knowledge would greatly speed up the process of drug discovery, with connections being drawn quickly between diseases and genes allowing for more concentrated discovery efforts. While the completion of the project certainly has helped in the discovery of the genetic basis for a number of diseases, the leap to drug discovery has been slower. A new study out of Switzerland, published in this week’s Proceedings of the National Academy of Sciences, is aiming to begin to bridge that gap, using genome wide association to identify memory-modulating drugs that could help treat conditions like post-traumatic stress disorder.

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Source: news.nationalgeographic.com

The group examined a sample of 1,802 healthy Swiss adults to find those genes associated with the formation of strong aversive memories. Aversive memories are those memories that carry a negative response which when triggered are meant to warn us away from the new stimulus (an extreme example would be a flashback, where some stimulus completely recreates the original negative memory; a more average one would be the sight of a bee if you’ve been stung before). The group found two genetic pathways connected to strong aversive memories, a neuroactive ligand-receptor interaction (a ligand being anything that interacts with a receptor) and a pathway associated with long-term depression. They then replicated their work with another group of 781 healthy adults and found twenty genes within these two pathways that were linked to aversive memory in both sample populations.

The group then took these twenty possible genes and looked at whether or not there were any drugs already known to interact with their products. They found fifteen that did and then continued to narrow the field down to nine candidates that had mild side-effects, were legal in Switzerland, and were easy to administer. They then examined a group of 349 severely traumatized patients to find any possible connections between their nine suitable candidates and the formation of extreme aversive memory. HRH1, a histamine receptor, proved to be their link.

Using the antihistamine diphenhydramine, the group ran a double blind study and found that their new treatment was able to reduce aversive memory formation, while neutral and positive reactions remained unaffected. An interesting sidenote: there was only significant reduction in aversive response to stimulus when the individual reported drowsiness caused by the diphenhydramine. When there was no sleepy side-effect, there was no impact on memory.

More work needs to be done to understand how this could help people with disorders based around aversive memories (such as PTSD), but this could lead to serious benefits for those haunted by the traumas of their past. This is also an impressive proof-of-concept study for drug discovery using genome-based analysis. There has been a lot of talk about how much the Human Genome Project and next generation sequencing advances could help bring new treatments to patients much quicker, but a startling lack of work done to actually accomplish that. With this study though, it’s clear that researchers are moving towards the integration of this new information into their ongoing work.

Original article:

http://www.pnas.org/content/110/46/E4369.full

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