Tourette syndrome research highlights 2015

Cheryl A. Richards, Ph.D. (1,2),* Kevin J. Black, M.D. (1,3-5) (ORCiD)

Departments of (1) Psychiatry, (2) Medicine, (3) Neurology, (4) Radiology, and (5) Neuroscience, Washington University School of Medicine, St. Louis, Missouri, USA

* Address correspondence to Dr. Richards at Campus Box 8134, 660 S. Euclid Ave., St. Louis, Missouri, USA or RichardsC@WUSTL.edu.

AbstractWe present selected highlights from research that appeared during 2015 on Tourette syndrome and other tic disorders. Topics include phenomenology, comorbidities, developmental course, genetics, animal models, neuroimaging, electrophysiology, pharmacology, and treatment. We briefly summarize articles whose results we believe may lead to new treatments, additional research or modifications in current models of TS.

Introduction

This article is the second in the TS Research Highlights series (Richards and Black, 2015). These articles are meant to disseminate recent scientific progress on Gilles de la Tourette Syndrome (TS). During each year, the article will be a work in progress, maintained as a web page on the Authorea online authoring platform (the working draft for 2016 appears here). After the calendar year ends, the article is finalized and submitted as the annual update for the Tics channel on F1000Research (Black, 2014).

Methods

We searched PubMed on 22 Jan 2016 using the search strategy: ("Tic Disorders"[MeSH] OR Tourette NOT Tourette[AU]) AND 2015[PDAT]. This search returned 202 citations and includes articles appearing online in 2015 but not officially published by year end (from journals that still focus on the paper user interface). We also reviewed F1000Prime recommendations and presentations of interest at selected medical conferences. Articles were chosen based on a purely subjective assessment of interest, guided by our judgment of possible future impact on the field. Some sections conclude with short tables listing additional articles.

Results

Phenomenology and natural history

Tic suppression

Since tic suppression is part of the treatment protocol for the Comprehensive Behavioral Intervention for Tics (CBIT) and for Exposure and Response Prevention, there has been increased interest in investigating the characteristics of tic suppression and the factors that affect it. A study of 26 TS adolescents compared free ticcing with a tic suppression condition (Ganos et al., 2015). During the free ticcing condition, tic distribution across body locations was consistent with the view that most tics occur at the level of the shoulders and above: eye tics were the most frequent, followed by facial/cervical tics, and those involving the arms and legs. Tics involving the trunk were the least common. During the tic suppression condition, eye tics increased in 10 subjects, as did hand tics in 3 subjects. Tic suppression was most successful for tics in body locations generally associated with fewer tics, such as the legs and trunk. The authors suggest that tic suppression involves specific, rather than global, inhibition since some types of tics are easier to suppress than others. Historically, other categories have been used to classify tics, such as simple vs. complex tics and motor vs. phonic tics. The results of this study suggest that future research may benefit from including body location in tic analyses.

By definition, children with Tourette syndrome (TS) have had tics for over a year. They can often suppress their tics briefly and they do so more effectively when rewarded for successful suppression. It has not been known whether the ability to suppress tics develops only with practice over the years of having tics or whether the ability to suppress tics is present when tics initially occur. Greene and colleagues addressed this question in children whose tics had developed within the past few months (Greene et al., 2015). When children received tokens with monetary value for tic-free intervals, they had significantly more of these intervals compared to a baseline, unrewarded condition. This result suggests the possibility that behavior therapy for tics may work, at least for some children, even before TS can be diagnosed.

Most tic patients frequently try to suppress tics, but find suppressing them uncomfortable and distracting. However, those who are more satisfied with their ability to suppress their tics also report a higher quality of life (Matsuda et al., 2016).

Sensory phenomena

Premonitory urges are common in TS, are perceived as triggers for tics, and are as bothersome as the tics themselves to many people with TS. Premonitory urges have a sensory component and many TS patients also report sensory sensitivities. Researchers have been clarifying the nature of premonitory urges and attempting to determine the underlying causes of the sensory sensitivities.

Scores on the Premonitory Urge for Tics Scale (PUTS) and the University of São Paulo Sensory Phenomena Scale (USP-SPS) were significantly correlated with total tic severity, tic complexity and vocal tic scores in youth and adults with TS (Kano et al., 2015). The PUTS and USP-SPS scores were also correlated with scores on the Dimensional Yale-Brown Obsessive-Compulsive Scale. This study provides additional evidence that the association between premonitory urges and tics is complex and may be influenced by obsessive-compulsive tendencies.

Another study examined the association between premonitory urges and interoceptive awareness (Ganos et al., 2015a). Interoceptive awareness was measured by how well subjects were able to mentally track their heartbeats, without being able to take their own pulse, during a specific period of time. Interoceptive awareness, tic severity, and obsessive-compulsive symptom severity were used in a multiple regression to predict PUTS scores. Greater interoceptive awareness and tic severity were significantly associated with higher PUTS scores while OCD symptom severity was not. The authors suggest that high interoceptive awareness may lead people to set a low threshold for perception of their own internal physiological sensations and therefore cause them to interpret these sensations as an urge to tic. Interestingly, TS subjects had lower interoceptive awareness than controls, suggesting that this downregulation of interoception might reflect a compensatory process.

Symptoms and comorbidity

Recent research has again demonstrated the wide prevalence of TS-associated comorbities and is a reminder of the need to perform studies with large enough sample sizes to examine the effects of comorbidities on the dependent variables of interest.

A retrospective review of 1,000,000 people in the Taiwan National Health Insurance Research Database examined the association between epilepsy and TS (Wong et al., 2016). 1,062 children and adolescents with TS were matched on age and sex with a control group of 3,186 subjects. The TS group had an 18-fold increased risk of epilepsy compared to the control group; the risk was still elevated 16-fold after adjusting for comorbidities (i.e., bipolar disorder, depression, learning difficulties, autism, anxiety disorders, sleep disorders). The authors acknowledge the possibility that some tics may have been mistaken for seizures, given the nature of the data set, but these data do suggest an important hypothesis for future confirmation.

In a large study of psychiatric comorbidity in TS, approximately 800 families were recruited primarily from TS specialty clinics in four different countries over a 16-year period (Hirschtritt et al., 2015). A total of 1374 participants with TS and 1142 family members unaffected by TS were included.