New TS study finds parallel between humans and mice

The writer of this guest blog, Ethan Macdonald, is a researcher of Tourette Syndome and cognitive science at McGill University in Montreal, Canada, who had challenging TS symptoms during his adolescence.

The recent study ”Histidine Decarboxylase Deficiency Causes Tourette Syndrome: Parallel Findings in Humans and Mice” (Barlan et al., 2014) examined a rare mutation in humans with TS. So rare in fact, that it has only been identified in one gene family. This particular mutation works well for creating new animal models.

Unfortunately, since the mutation is rare, the findings from this study may not apply to much of the TS population (they especially might not apply to those whose symptoms decrease with age). That said, some articles (Karagiannidis et al., 2013) suggest that other histamine-related mutations are more prevalent in the TS population. This is hopeful: perhaps there could be some therapeutic overlap.

Genome-wide association studies (studies that take a look at many common genetic variants in different individuals to see if any variant is associated with a trait) have failed to identify common mutations for TS. Perhaps this is because of small sample sizes. In this study, no causal mechanism was found between genetics and human behavior. I would consider the title of the paper to be a bit overstated given this.

The researchers hypothesized that the family with the mutation had lower histamine levels, which lead to higher dopamine levels, which lead to more tics and that this could be replicated in a mouse.

Here are some key points from the study:

  • Indeed, the researchers found that mutated mice had an underlying susceptibility for tic-like behaviors;
  • Similar to humans with the mutation, the tic-like behaviors in mice didn’t change with age;
  • By injecting Haloperidol (a “dopamine blocker”), the researchers were able to reduce or eliminate the tic-like behaviors in mice;
  • This happens in humans, too;
  • By injecting histamine, the researchers were able to eliminate tic-like behaviors;
  • Dopamine levels dropped in the striatum after the injection of HA;
  • Using neuroimaging (PET), they found some evidence in humans that there is a direct relationship between the mutation and dopaminergic regulation in the basal ganglia; and
  • This is a very interesting mechanism, and it definitely supports their hypothesis, although we still don’t know exactly how it works or what the effects are outside of the basal ganglia.

The authors of this paper suggest that the findings are broadly generalizable to the TS population (meaning that findings apply widely to other people with TS). I would caution again that this is a very specific mutation found in only one family, although perhaps the results will apply to other people with similar mutations. Further research should be done to replicate these findings and determine for whom and to what extent histamine modulation affects tics in humans.

More broadly, this constitutes a new animal model of TS with testable hypotheses. It may or may not lead to new medications or neurological interventions for people with TS. I personally believe that this vein of research probably won’t help with the social or cognitive factors involved with TS, and future findings from this stream of research could complete part of the puzzle but not all of it.

If you would like more information about this article, please e-mail tsfc@tourette.ca.

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