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Kevin J. Black is an advisor for the F1000Research Tics collection. This collection provides a single portal to all the best research and clinical information on tics and tic disorders. Kevin gives us some background on Tourette Syndrome and the current research in this area.

Georges A. E. B. Gilles de la Tourette was a 19th-century physician who during his lifetime was primarily known for his studies of hysteria and hypnotism. His mentor, Jean-Martin Charcot, encouraged him to write a report on what they termed “convulsive tic disorder”, which was believed to be untreatable, chronic, progressive and hereditary. Charcot began to describe the condition as “Gilles de la Tourette’s tic disorder,” and this has turned out to be what Gilles de la Tourette is most known for now. In America, the most common name for the condition is an incorrect but simpler “Tourette syndrome.”

Tourette syndrome is defined as a childhood-onset condition without a systemic or other neurological cause

Tourette syndrome (TS) is defined as a childhood-onset condition without a systemic or other neurological cause that includes motor and vocal tics that collectively last for at least a year. Tics are repeated movements or noises inappropriate to the situation, and have traditionally been divided into simple vs. complex tics and motor vs. vocal (or phonic) tics.

Tics are most easily defined by example. Simple motor tics include head shaking, turning the eyes, and excessive or exaggerated blinking. Simple vocal tics include snorting, humming and grunting. Complex tics include patting objects, picking at irregular surfaces, and saying words or phrases. Although tics define TS, most patients in clinical care also have hyperactivity, impulsivity, inattention, obsessions or compulsions.

Only partial information is available about the cause of TS. The syndrome is strongly heritable, but a few environmental risk factors are known, such as birthweight and probably maternal smoking during pregnancy, and the heritable risk of TS appears to be polygenic.

Newer methods, and collaborative efforts enabling larger samples, have provided some important new leads.

The moment-to-moment severity of TS is a different matter, clearly influenced by the psychosocial setting. Tics are also at least somewhat suppressible by an effort of will. These characteristics lead to frequent misunderstandings by naive observers, who may wrongly conclude that the tics are performed intentionally to gain attention or to escape an unwanted obligation.

Current research hotspots

The known heritability of TS has led to repeated genetic studies that, until recently, were largely disappointing. In the past couple of years, newer methods, and collaborative efforts enabling larger samples, have provided some important new leads. One such study identified NRXN1 deletions (increasing the risk of TS by 20-fold) and CNTN6 duplications (10-fold. Both are genes encoding cell adhesion molecules that promote growth of neurites, and both have separately been implicated in genetic studies of autism. However, copy number variants (CNVs) in these two genes were present in only 1% of the patient sample, and the overall burden of CNVs, especially large, rare CNVs, was much higher in the TS sample, suggesting that numerous genes contribute to the heritability of TS.

The severity of TS naturally fluctuates over time, so that randomized controlled trials are essential to demonstrate efficacy.

Neuroimaging studies in TS involve important methodological difficulties related to large data sets, head movement and symptoms other than tics, but various investigators have addressed these directly, and larger, collaborative studies have begun. Finding a face-valid animal model of TS (i.e., movements that convincingly are tics rather than other abnormal movements) is another important area of research. The Tics channel’s recent summary of TS research from 2016 discusses both of these topics.

Treatment research is also active and includes novel psychotherapeutic approaches as well as a variety of medications. Something like 100 different treatments have been tested in TS over the years. Several have proven efficacious, including dopamine receptor antagonists and a behavior therapy package called comprehensive behavioral interventions for tics (CBIT).

Unfortunately, none of the available treatments improve symptoms by more than about 50% when averaged across patients. Furthermore, the severity of TS naturally fluctuates over time, so that randomized controlled trials are essential to demonstrate efficacy.

Looking ahead

Making predictions can be difficult, but here are four of my predictions about strong prospects for the future.

Online tools and smartphone apps to reduce tic burden will be further researched and will become important in treatment.

I’ve heard my geneticist colleagues make the case rather convincingly that the field is on the brink of further progress in understanding the genetics of TS. This is due in part to the increasingly large samples available for genetic studies and in part to different statistical approaches more suitable for conditions influenced by numerous genes.

Online tools and smartphone apps to reduce tic burden will be further researched and will become important in treatment. The web site www.TicHelper.com, a commercial site developed with NIH funding by leaders in the field, just went live at the beginning of this month, and other efforts on electronic platforms are also under way.

Large, collaborative efforts will become increasingly important for neuroimaging studies

Neurosurgical treatment for TS will become more nuanced, with ongoing work on optimal site selection, closed-loop adaptive deep brain stimulation, current steering, and even non-invasive stimulation.

Large, collaborative efforts will become increasingly important for neuroimaging studies of TS. My colleagues and I are involved in one such initiative with colleagues from UCLA, France and the UK. The ENIGMA network is also exploring an international initiative into the genetics of the development of brain structure in TS using MRI.

The current research landscape in Tourette Syndrome provides a good basis for optimism. If you are interested in publishing your research on this topic you can submit to the Tic collection here.