Advancements in the Phenomenology, Assessment, and Treatment of Tourette Syndrome

Abstract

Purpose of the Review.

Tourette Syndrome and chronic tic disorders, collectively referred to as TS, are relatively common childhood onset neuropsychiatric conditions associated with functional impairment and distress. Over the past several years, clinical research has contributed to the advancement of the field’s understanding of mechanisms and clinical correlates of TS. This progress has led to the development of key assessment tools and the implementation of novel interventions for individuals with TS.

Recent Findings.

This article provides a review of innovative TS research focusing on four key themes: (1) investigation of clinical phenomenology of TS; (2) validation of assessment tools for TS; (3) dissemination of current evidence-based treatments for TS, and (4) exploration of new intervention programs.

Summary.

Cumulatively, this growing body of work presents considerable progress and provides a path forward to improve the assessment and treatment of TS.

Introduction

Tourette Syndrome and other persistent tic disorders (collectively referred to as TS) are childhood onset neuropsychiatric conditions characterized by involuntary motor and vocal tics (1). While tics are the most overt symptom of TS, individuals with TS also experience aversive somatosensory sensations that precede tics called premonitory urges (1,2). Additionally, individuals with TS commonly experience challenging, co-occurring affective states [e.g., anxiety, irritability, anger (3–5)] and psychiatric comorbidity [e.g., anxiety disorders, attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD) (3,6,7)]. Collectively, tics, premonitory urges, psychiatric comorbidities, and co-occurring difficulties with emotion regulation can contribute to significant impairment and reduced quality of life for many individuals with TS (8). While effective interventions for TS exist [i.e., behavior therapy, pharmacotherapy; (9,10)], there is a critical need to understand the underlying mechanisms and improve upon assessment tools and evidence-based treatments (EBT) for individuals with TS in order to enhance patient outcomes (11). Over the past several years, there have been considerable advancements in the field’s understanding of phenomenology, assessment, and treatment of TS. This paper provides an overview of TS and discusses some of the promising advances in the field. These advances include: (1) promising new treatment targets for TS—including urge intolerance and emotion dysregulation; (2) updates to evidence-based assessment of TS symptomatology; (3) exploration of mechanisms for evidence-based treatments; and (4) identification of interventions that address novel treatment targets for patients with TS. This review highlights directions for future clinical research which will ultimately improve evidence-based care and help patients with TS achieve optimal clinical outcomes.

Phenomenology of TS

While the broad phenomenology of TS has been well-documented, recently there has been greater investigation and advancement in our understanding of premonitory urges and constructs underlying comorbid conditions, such as emotion dysregulation, that can serve as therapeutic targets for individuals with TS.

Premonitory Urges

Premonitory urge sensations are common somatosensory sensations that are observed across both youth and adults with TS (1,2). Individuals with TS often experience an uncomfortable premonitory urge prior to ticcing, and feel a sense of relief from the urge after tic expression. This urge → tic → relief cycle is theorized to reinforce and maintain tic expression over time (2). In behavior therapy, premonitory urges (among other internal and external factors that can contribute to tic expression) serve as a primary site for intervention (12). Here, individuals with TS learn to build awareness to tics and associated antecedents (e.g., urges) and implement behavioral strategies to inhibit tic expression contingent upon antecedents (12). This disrupts and ultimately discontinues the reinforcement cycle maintaining tic expression. Clinical research suggests that greater levels of premonitory urges are related to higher levels of tic severity, and are associated with poorer levels of quality of life among individuals with TS (13).

Urge Intolerance.

One clinical construct that may serve as a promising mechanism of change for TS symptom severity is urge intolerance. Urge intolerance can be described as an individual’s difficulty with tolerating premonitory urges (14,15). Higher levels of urge intolerance predict greater levels of tic severity and tic impairment among youth and adults with TS (14,15). Lower tolerance to distressing premonitory urges may explain, in part, the limited treatment response to behavior therapy experienced by some patients with TS. For instance, individuals who have low tolerance to distressing premonitory urges may struggle to effectively implement tic inhibition skills, impeding treatment progress in behavior therapy. Houghton and colleagues (16) found that reductions in premonitory urge severity alone did not mediate symptom reductions among youth and adults with TS who received the Comprehensive Behavioral Intervention for Tics (CBIT). These findings suggest that alternative change processes, such improvements in tolerance of premonitory urge sensations, may be important for understanding mechanisms that drive symptom change in behavior therapy for TS. If so, interventions that enhance distress tolerance to premonitory urges could help individuals with TS better implement therapeutic skills to inhibit tics and ultimately discontinue the reinforcement cycle maintaining tic expression over time (17).

Interoceptive Awareness.

Another putative treatment target may be interoceptive awareness, which refers to an individual’s ability to sense, interpret, and respond to internal physiological states within their own body. Some research suggests that dimensions of interoception have been found to predict premonitory urges and tic severity among individuals with TS (18), while other sources contend that interoceptive sensitivity is an independent, but clinically relevant, construct among populations with TS (19). Relative to healthy adults, adults with TS experience greater general body awareness and anxiety-associated somatization (20). Furthermore, evidence suggests that greater body awareness was significantly associated with greater premonitory urge severity (20). Uaeda and colleagues theorize that premonitory urge phenomena in TS may represent enhanced or aberrant interoceptive sensations (21). Future studies investigating the relationship between interoceptive awareness and TS symptomatology are warranted, as somatosensory awareness may play an important role in the inhibition of tic expression.

Emotion Dysregulation

Emotion dysregulation is a common challenge that underlies many forms of psychopathology (22)—including conditions that commonly co-occur with TS (e.g., OCD, ADHD). Difficulties with emotion regulation are thought to contribute to both tic- and non-tic related impairment among individuals with TS (23). Similar to premonitory urges, affective states (e.g., stress, frustration) are theorized to contribute to increases in tic expression (4,24). Consequently, clinicians often will work with individuals with TS to identify emotional states that serve as antecedents to tic expression, and to implement adaptive coping strategies (e.g., relaxation strategies to address feelings of stress that precede tics in behavior therapy) to better regulate emotions and reduce the expression of tic symptoms (12).

In the past five years, clinical research on emotion regulation among individuals with TS has expanded. Quast and colleagues (25) found that, among a sample of youth with TS, emotion regulation mediated the relationship between clinician-rated tic severity and tic-related social impairment. Building off of this work, Ramsey and colleagues (23) found that greater levels of affect lability predicted higher levels of clinician-rated tic and non-tic related impairment after controlling for clinician-rated tic severity among youth with TS. Above and beyond clinician-rated tic severity, greater levels of affect lability and tic impairment uniquely predicted higher levels of family accommodation (23). In a sample of 60 youth with TS, Rurhman and colleagues (26) reported that emotion dysregulation was significantly related to both tic severity and severity of comorbid internalizing psychiatric conditions. Furthermore, emotion regulation difficulties mediated the relationship between the perceived stress of youth with TS and both TS and non-TS comorbid symptom severity (26). Specifically, greater levels of stress predicted greater levels of emotion regulation difficulties which, in turn, predicted greater levels of psychiatric symptom severity. Taken together, these findings suggest that supplementing evidence-based behavior therapy with strategies that enhance emotion regulation may improve clinical outcomes for individuals with TS.

Assessment of TS

As the field gradually expands its knowledgebase of the phenomenology of TS, clinicians and researchers have incorporated these advancements to improve the evidence-based assessment of TS across tic severity, premonitory urge severity, and detecting response to interventions.

Assessing Tic Severity

While many measures have been used to evaluate tic severity [see (27) for a comprehensive review], the Yale Global Tic Severity Scale (YGTSS) (28) is recognized as the gold-standard outcome measure in clinical trials for TS. The YGTSS is a clinician-administered semi-structured interview that assesses for the presence and severity of vocal and motor tics over the course of the past week (28). The YGTSS is comprised of a Symptom Checklist that inquires about the presence of common motor and vocal tics. The Symptom Checklist is used to guide ratings on the Severity Scale, where motor and vocal tics are rated separately across five domains (number, frequency, complexity, intensity and interference) using a 0 to 5 rating scale. Severity items are summed to produce separate Motor (range 0–25) and Vocal (range 0–25) tic scores that are summed to produce a Total Tic Score (range 0–50). The YGTSS includes a single item that assesses tic-related impairment (Impairment Scale, range 0–50). The YGTSS has demonstrated strong psychometric properties (29), and has been found to be sufficiently sensitive to detect treatment effects from both behavioral (30,31) and pharmacological (32,33) interventions. In a large sample of over 700 youth with TS, the YGTSS demonstrated adequate internal consistency, along with acceptable convergent validity and good divergent validity (34). Here, the YGTSS was highly correlated with the Clinical Global Impression (CGI) scale for tics; conversely, the YGTSS demonstrated only low-to-medium correlations with severity ratings of other psychiatric symptoms (34). The YGTSS has also been translated into languages other than English, and has demonstrated good psychometric properties among Chinese youth with TS (35).

While the YGTSS has demonstrated strong psychometric properties, clinical research suggests that some modifications to the instrument may be appropriate (34,36). In recent years, the YGTSS has been updated to enhance the precision of tic severity assessments. The Yale Global Tic Severity Scale- Revised (YGTSS-R) includes minor revisions to anchor point descriptions for three Severity dimensions (e.g., Frequency, Complexity, and Interference) to promote full use of scales for these dimensions, as well as an expanded Vocal Tic Symptom Checklist (36). It is important to note that these revisions do not negate prior work using the measure, but rather enhance the precision of its use moving forward.

Assessing Premonitory Urge Severity

Given their theorized role in the maintenance and treatment of tic expression, the accurate assessment of premonitory urges is critical in order to characterize TS symptom presentation. Premonitory urges are commonly assessed via the Premonitory Urge for Tics Scale (PUTS), a 10-item self-report, that uses 9 of the 10 items to measure global premonitory urge severity (37). While the original, English-language version of the PUTS has demonstrated good psychometric properties (37), recent investigations have taken strides to translate and validate the instrument across cultures. Thus far, there have been promising results for Chinese- (35) and Spanish- (38) language versions of the PUTS among youth with TS. Building off of the PUTS, McGuire and colleagues developed and validated the Individualized Premonitory Urge for Tics Scale (I-PUTS), a clinician-report instrument that captures the presence, frequency and intensity of premonitory urges associated with individual tics (39). The I-PUTS has been shown to exhibit good psychometric properties (39), and has been translated and validated in a Chinese sample of youth with TS (40).

Monitoring TS Treatment Response

In addition to augmenting the precision of TS assessment, steps have been taken to better characterize treatment response for individuals with TS (41–44). In clinical trials, a common metric to determine a treatment response is the CGI-Improvement (CGI-I) (45), which is administered by an independent evaluator who is masked to treatment condition. Research suggests that a 25% reduction of the YGTSS Total Tic Score corresponds with a treatment response on the CGI-I (41,43). While use of the CGI-I is relevant to clinical trials, this approach does not generalize well to “real world” community practice due to the level of training, expertise, and quality assurance monitoring required. In response, efforts have been made to determine a range of improvement on clinical assessment scales of TS. McGuire and colleagues (44) examined benchmarks of tic severity and impairment using the YGTSS and CGI, finding that predictive models using YGTSS scores produced only moderate agreement with CGI ratings in their investigation. McGuire and colleagues (44) conclude that YGTSS scores, relative to CGI ratings, characterize overall TS severity well, are not influenced by common psychiatric comorbidities, and are not impacted by clinician’s experience (or lack thereof) with TS. Therefore, the YGTSS can serve as a helpful tool for guiding treatment recommendations for clinicians who are less experienced with TS (44). Research has also examined the link between clinician measures and parent ratings of tic severity. Ricketts and colleagues (42) implemented signal detection analyses of the Parent Tic Questionnaire (PTQ) to benchmark treatment response. Results demonstrated that a 10-point decrease (55% reduction) in the PTQ total score was associated with a clinically-significant treatment response for youth with TS (42).

Evidence-Based Interventions for TS

Evidence-based treatment guidelines for TS support two types of interventions: behavior therapy and pharmacotherapy (9,10,46). Pharmacotherapy for TS has been well investigated, with meta-analyses reviewing the extant literature and documenting treatment effects (47,48). While efficacious, pharmacological treatments for TS are accompanied by adverse health effects (e.g., sedation, weight gain) that often result in discontinuation (49). Treatment guidelines universally recommend behavior therapy—including interventions such as habit reversal training (HRT) and CBIT [see review (49) for more detail on behavioral interventions for TS] — for moderate tic severity, and pharmacotherapy with behavior therapy for severe tic severity (9,10,46).

Behavioral interventions are designed to disrupt the cycle of negative reinforcement involved in tic expression (11,49). In behavior therapy, individuals with TS learn to build awareness to tics and associated antecedents (e.g., urges, stress responses and their corresponding affective states) and implement behavioral strategies (e.g., competing response) to inhibit tic expression contingent upon antecedents (12). Patients receiving CBIT work with a clinician to learn core components of HRT such as psychoeducation about TS, awareness training for tics and their associated antecedents, competing response training to inhibit the expression of tics, and social support to practice and reinforce the use of therapeutic skills. Additionally, CBIT includes therapeutic skills modules, such relaxation training and functional assessment/intervention, to address internal and external factors that influence tic expression (12). In relaxation training, patients learn specific skills (i.e., diaphragmatic breathing, progressive muscle relaxation) to manage stress—a factor that commonly increases tic expression. The functional assessment evaluates situations and environments (i.e., antecedents) that exacerbate tic severity, and defines the outcomes of those situations when tic expression is worse (i.e., consequences). Building on this assessment, the functional intervention aims to apply functional strategies to decrease antecedents that exacerbate tic expression, and reduce consequences that may unintentionally maintain and/or worsen tic expression over time.

Given its efficacy and safety profile, behavior therapy is considered to be a favorable treatment option and is recommended as a first line of treatment for TS for individuals with TS (9,10,46). Research has explored a number of factors that may predict patients’ treatment response to behavioral interventions for TS, such as CBIT. While research (50) suggests that age is not a significant moderator of behavior therapy treatment response rates among individuals with TS, clinical trials research have shown marginally lower treatment response rates among adults relative to children with TS (30,31). However, behavior therapy for TS is considered to be efficacious for individuals from 5 (51) up to 75 (52) years of age.

Given the tic specific nature of behavioral interventions for TS, it might be anticipated that specific tics and/or tic groupings would exhibit a differential therapeutic improvement. Cluster analysis suggests varied tic symptom profiles respond equally well to CBIT across child and adult patients with TS (53). When conducting a more individualized analysis of tics, several interesting findings were identified (54). First, tics that had premonitory urges responded better to behavior therapy relative to supportive therapy. Second, while both motor and vocal tics were more likely to improve with behavior therapy, several tics exhibited significant improvement (e.g., eye blinking, head movements, mouth movements, complex motor combinations, sniffing, and throat clearing) and were even more likely to remit (e.g., complex motor combinations, throat clearing) when treated with behavior therapy relative to supportive therapy.

When examining the influence of co-occurring psychiatric conditions on behavioral interventions, the evidence is mixed. A meta-analysis found that the presence of co-occurring ADHD in participants with TS was associated with smaller treatment effects (55). However, in a combined sample of 248 children and adults who received CBIT or supportive therapy, the presence of comorbid ADHD, OCD, or anxiety did not significantly moderate patients’ treatment response to CBIT (50).

Beyond tic characteristics and psychiatric comorbidities, investigations have explored other treatment moderators. Several studies have examined the role of cognitive capabilities predicting behavior therapy outcomes for individuals with TS (56–58), with mixed findings suggesting that baseline inhibitory control may predict tic severity reductions (58). Additionally, results across clinical trials found that the presence of tic medication moderated patients’ response to behavioral intervention (50). Although patients demonstrate greater tic reduction in CBIT compared to the supportive therapy condition regardless of medication status, clinical improvements were greater for patients who were not taking tic medications. However, it is important to note that these findings do not suggest that patients on a tic medication would not benefit from behavior therapy. Instead, the therapeutic benefit of behavior therapy may not be as robust among patients on a tic medication due to tic reductions already achieved by medication. Continued efforts are needed to identify key mediators and moderators that can enhance behavioral treatment response for patients with TS.

In cases of positive therapeutic response in child and adult populations with TS, the effects of behavior therapy are maintained up to 6-months (31,59,60). Promisingly, youth who respond to behavior therapy for TS in childhood have been found to continue to benefit from this treatment in adulthood—demonstrating the potential of this intervention to alter the developmental trajectory of TS across the lifespan (61). Despite the efficacy of behavior therapy, many patients remain symptomatic following this EBT (11). Clinical trials suggest that only ≈50% of youth and ≈40% of adults with TS respond to behavior therapy for tics (30,31). Moreover, behavior therapy predominantly reduces tic severity and does not address other commonly comorbid conditions and/or underlying constructs of TS [e.g., emotion dysregulation; (12,59)]. Thus, research has focused on both enhancing behavior therapy for TS, but also investigating new treatments—particularly for adults who have lower behavior therapy response rates.

Advancements in Behavior Therapy for TS

In order to improve clinical outcomes for patients with TS, further clinical research is needed to better understand mechanisms to optimize behavior therapy outcomes, and also increase access to optimized behavior therapy in a scalable and sustainable manner (62). This line of research would inform the development and refinement of therapeutic approaches to better target, engage, and optimize identified mechanisms, and ultimately improve clinical outcomes for patients with TS. In regards to elucidating key mechanisms of behavior therapy, leading candidate targets focus on reduction of premonitory urge severity (62). However, as noted earlier, reductions in premonitory urge severity do not entirely mediate tic severity reductions (16). Given that reinforcement cycles are the primary target of behavior therapy, associative learning processes may also be an important therapeutic target as well (62). Broadly, associative learning occurs when a behavior becomes associated with an outcome, which increases the probability of the future occurrence of that behavior (53). For instance, in the case of negative reinforcement learning (a type of associative learning process), relief from an uncomfortable premonitory urge sensation following a tic occurrence consequently increases the likelihood of expression of the tic in the future. Indeed, initial investigations have found that augmenting associative learning with d-cycloserine (DCS) can enhance tic severity reductions in a Quick-Win/Fast-Fail clinical trial (63). DCS is an N-methyl-D-aspartate (NMDA) partial agonist that affects the glutamate system; it has been found to enhance associative learning in several clinical trials (64). Findings from this investigation suggest that DCS effectively enhanced reinforcement learning in youth with TS, strengthening the new (urge-no tic) association relative to the old (urge-tic) association (63). Other promising mechanistic targets— such as urge intolerance, somatosensory awareness, and emotion dysregulation— described earlier in the phenomenology of TS section warrant further clinical trial research to gauge their influence on TS outcomes. Among these three putative mechanisms, urge intolerance represents the most promising with current treatment investigations underway.

While it is important to identify therapeutic mechanisms that enhance clinical outcomes, it is equally important to identify therapeutic components that do not improve TS symptoms. Peterson and colleagues (65) found in a small multiple-baseline case series that relaxation training alone was not effective in reducing tic severity among youth with TS; however, relaxation training was found to be beneficial when included in conjunction with other elements of CBIT (i.e., habit reversal training).

Finally, as behavior therapy mechanisms and treatment protocols are optimized, it is essential to increase the accessibility of these treatments to patients with TS. Unfortunately, critical barriers continue to limit patient-access to empirically-supported behavioral interventions for TS (11). Dissemination research has begun to explore innovative adaptations to behavior therapy in order to increase patients’ access to EBT. Several investigations are underway to explore possible treatment modalities towards this goal, including examining the utility of group-based behavior therapy for TS (66), as well as the merit in technology-based applications of behavior therapy for youth and adults with TS (67,68). Promising work has also adapted behavior therapy treatment protocols to be suitable for youth with TS as young as 5 years old (69). This line of research allows for more patients with TS to access EBT, thereby reducing functional impairment and improving quality of life.

New Treatments for TS

There is a critical need for new treatments for individuals with TS that are efficacious for reducing tic severity, beneficial for co-occurring conditions, and have few adverse health effects. Novel intervention protocols that incorporate third-wave cognitive behavioral therapy elements, such as mindfulness, may prove beneficial for improving urge intolerance and emotion regulation among individuals with TS. Research has demonstrated that mindfulness-based interventions have been beneficial to a wide array of clinical populations, including individuals with psychiatric conditions (70). On an encouraging note for treating tics and co-occurring TS phenomenology, mindfulness-based interventions have demonstrated efficacy for reducing stress and teaching individuals how to sit with uncomfortable sensations, thoughts, and emotions rather than trying to escape or change them (71). Early clinical trials of a mindfulness-based stress reduction (MBSR) intervention for tics found that adolescents and adults with TS experienced reductions in self-reported functional impairment [work, social (72,73)]. Further research is needed to explore the impact of these promising interventions on both tic-related clinical outcomes and co-occurring challenges (e.g., psychiatric comorbidity, emotion regulation challenges) in order to improve the quality of life for patients with TS.

Conclusion

This review summarizes a number of exciting advancements in the field’s understanding of the phenomenology, assessment, and treatment of TS. Recent work characterizing individuals with TS’ experience of premonitory urge phenomena and emotion dysregulation offer promising new treatment targets. Improvements in clinical assessment, from the validation of the YGTSS in large samples to the translation and cross-cultural validation of TS-specific measures, allow for clinicians and researchers alike the opportunity to implement high quality, evidence-based assessments. Clinical outcome research supports the long-term efficacy of first-line behavioral treatments for TS, but more work is underway to delineate treatment mechanisms and identify interventions that address novel treatment targets for patients with TS. Ultimately, this line of research will provide a pathway to improve current EBT and help patients with TS experience optimal clinical outcomes.

Key Points.

• Tourette’s syndrome and other persistent tic disorders (collectively referred to as TS) are characterized by motor and vocal tics that cause significant impairment across the lifespan.

• In addition to tics, individuals with TS experience co-occurring clinical phenomenology such as difficulty tolerating premonitory urges (urge intolerance), somatosensory sensitivity, and emotion regulation challenges— all of which serve as putative treatment targets for new TS interventions.

• Evidence-based assessment of the features of TS— including use of validated instruments such as the YGTSS and PUTS— is essential in order to characterize patients’ clinical presentations and allow clinicians the opportunity to apply best practice treatment recommendations.

• Behavior therapy for TS (e.g., CBIT) is considered to be a first-line treatment; however, further research is needed to understand treatment mechanisms and disseminate this protocol.

• Clinical research is needed to develop and evaluate novel interventions for patients with TS (e.g., mindfulness-based treatments), to address both tic-specific and co-occurring challenges, in order to improve patient outcomes.