Co-Occurring Anxiety in Youth with Tic Disorders: A Review

Abstract

Objective:

To review the current state of the literature regarding anxiety symptoms and anxiety disorders in chronic tic disorder (CTD).

Results:

We conducted a literature search on anxiety and tic disorders. Anxiety symptoms and anxiety disorders are common in youth with CTD, with ∼30%–50% of youth with CTD having at least one co-occurring anxiety disorder. Tics often improve by young adulthood but anxiety symptoms tend to persist, or worsen, over time. Anxiety and tics are closely related, but the exact nature of their relationship is poorly understood. We discuss some potential ways in which anxiety and tics are linked with an emphasis on the underlying brain circuitry involved. The relationship between anxiety and tics may be related to the premonitory urge. In addition, stress hormones may link anxiety and tics. Individuals with CTD have greater activation of their hypothalamic-pituitary-adrenal system in response to acute stress. We also review the impact of anxiety on youth with CTD and approaches to management of anxiety in youth.

Conclusions:

Anxiety is common in youth with CTD, is associated with more severe CTD, and can adversely affect a child's function. Thus, it is important to identify anxiety disorders in CTD and manage them appropriately.

Introduction

Chronic tic disorders (CTDs) are common neurodevelopmental disorders, affecting 2%–3% of youth (Tinker et al., 2022). Diagnosis is based on childhood onset of tics with persistence for at least 1 year (American Psychiatric Association, 2013). This group of disorders includes chronic motor tic disorder, chronic phonic tic disorder, and Tourette disorder (TD); diagnosis is based on the types of tics present. In a study of 1374 individuals affected by TD and 1142 unaffected first-degree relatives from 802 independent families recruited from tic disorders specialty clinics across a variety of sites, phenotypic data collected between 1992 and 2008 showed that ∼90% of individuals with CTD have at least one co-occurring neuropsychiatric condition (Hirschtritt et al., 2015).

Attention-deficit/hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD) are considered core features of CTD and share a genetic relationship with tics (Hirschtritt et al., 2015). ADHD and OCD have been the subject of extensive research in the tic community. However, non-OCD anxiety disorders, which are also common in CTD, are increasingly recognized as important contributors to the overall impact of tic disorders. In this article, we review what is known about non-OCD anxiety in CTD and discuss areas for future research.

Methods

We used PubMed, searched for anxiety and tic disorder, anxiety and Tourette, stress and tic disorder, and stress and Tourette, as well as co-occurring conditions and brain circuitry in anxiety and Tourette. We only included those that included information about anxiety.

Epidemiology of Anxiety Disorders in CTD

Anxiety disorders are defined by excessive fear, or negative emotions, out of proportion to the stimulus, that cause impairment or distress to the individual. Anxiety disorders are the most commonly diagnosed mental illness in youth, present in ∼10%–20% of the general pediatric population (Salum et al., 2013). There are many types of Anxiety Disorders, diagnosed based on the types of symptoms and inciting stimuli. OCD used to be considered a type of anxiety disorder but, in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, it has been reclassified into a separate category, Obsessive-Compulsive Spectrum Disorder (American Psychiatric Association, 2013).

Anxiety disorders are common in individuals with tics, as demonstrated in both community and clinical settings. In a community-based study, researchers evaluated for the presence of tics in youth within a school setting (Kurlan et al., 2002). Psychiatric disorders were compared between those with and without tics and, for most of the anxiety disorders evaluated, anxiety disorders were nearly twice as likely to occur in the tic disorder group as the nontic group. However, the participation rate in this study was 11%, so the sample may not have been random and participants may have differed from nonparticipants. In a study of 190 youth with TD referred to a tic disorder clinic, the majority of subjects had at least one anxiety disorder (Coffey et al., 2000). Across multiple studies with varied samples, ∼30%–50% of individuals with CTD have at least one co-occurring anxiety disorder (Bitsko et al., 2014; Coffey et al., 2000; Kurlan et al., 2002).

All the studies had different samples with different ascertainment, but they have all been included in this article to better explain the range of findings. In CTD, anxiety disorders are more common in those with co-occurring OCD (Hirschtritt et al., 2015). However, even when controlling for OCD and ADHD, CTD is associated with increased rates of anxiety disorders. It is possible that anxiety is more common than these prevalence estimates suggest. Patients who do not meet criteria for a formal diagnosis of an anxiety disorder may nonetheless have impairing anxiety symptoms (Lewinsohn et al., 2004; Marwitz and Pringsheim, 2018; Safer et al., 2015). In a sample of youth with TD, fewer than 2% met formal diagnostic criteria for a diagnosis of Separation Anxiety Disorder based on interview but >30% met clinical significance for these symptoms (Marwitz and Pringsheim, 2018) based on the Multidimensional Anxiety Scale for Children (MASC) (March et al., 1997), a validated self-report instrument for anxiety.

Sex differences may exist for anxiety in CTD. Anxiety disorders are significantly more common in girls compared with boys (Hirschtritt et al., 2015). In addition, female sex is associated with future emotional disorders such as anxiety disorders in individuals with TD (Groth et al., 2019). Females with TD are more likely than males with TD to report tics leading to the development of anxiety (Lewin et al., 2012). Despite these reported sex differences, a recent cross-sectional study did not find any significant differences between sexes in terms of anxiety rate or severity (Girgis et al., 2022).

CTD is genetically related to OCD and ADHD (Hirschtritt et al., 2015; Mathews and Grados, 2011), but thus far, evidence has not supported a direct genetic relationship between CTD and anxiety disorders. Heritability analyses have demonstrated that, while anxiety disorders were genetically associated with CTD, this relationship was no longer significant when controlling for co-occurring OCD and ADHD (Hirschtritt et al., 2015). Of interest, there was a significant relationship between anxiety disorders and ADHD (Hirschtritt et al., 2015). In addition, parental history of ADHD was associated with increased rates of psychiatric co-occurring disorders, such as anxiety disorders (Hirschtritt et al., 2015). Thus, anxiety disorders may be more genetically related to co-occurring ADHD than to CTD itself.

Although a genetic relationship between CTD and anxiety disorders has not been clearly established, anxiety disorders are common in families of children with CTD. In a case–control study of parental psychiatric disorders and CTD in offspring, maternal psychiatric disorders were strongly associated with CTD in the offspring (Leivonen et al., 2017). The odds of having a child with CTD was approximately two to three times as high in those with any maternal psychiatric disorder, including maternal anxiety disorders. Paternal psychiatric disorders were also associated with CTD. The odds of having a child with CTD was nearly twice as high in those with paternal anxiety disorders when adjusting for maternal psychiatric diagnoses.

Clinical Course of Anxiety in CTD

Compared with the general pediatric population, anxiety disorders may have an earlier onset in youth with CTD. In a study of >1300 subjects with TD, age at onset of tics and co-occurring conditions was assessed across the lifespan (Hirschtritt et al., 2015). Median age at onset of TD was 6 years, and anxiety disorders typically started within a year of tic disorder diagnosis (Hirschtritt et al., 2015). Age at highest risk for onset of anxiety disorders was broad, starting at 4 years and extending into adolescence. Age at onset may be later in girls compared with boys (Hirschtritt et al., 2015). Childhood onset of anxiety is associated with a higher prevalence of tic disorders compared with adolescent onset of anxiety (Doering et al., 2022). However, although anxiety disorders may start early in this population, it is important to continually screen for them for all youth with CTD, regardless of age.

For many individuals with CTD, tics improve by later adolescence or young adulthood. In a literature review of prognosis in tic disorders, approximately one third of individuals report tic improvement and one third report no tics by young adulthood (Bloch and Leckman, 2009). In objective assessments of tics in young adulthood, the majority of individuals with CTD have persistent but improved tics. Of interest, half of those who reported being tic-free were noted to have tics during videotaped assessments (Pappert et al., 2003). Thus, although individuals may perceive themselves as being tic-free, tics typically persist. Although tics may often improve—objectively or subjectively—in older age groups, emotional symptoms including worrying, being clingy, having many fears, having somatic symptoms, and being unhappy as assessed by the Strengths and Difficulties Questionnaire (Van Roy et al., 2008) tend to persist and may worsen.

In a prospective community-based study assessing children 4 years apart, parents and teachers of youth with tics reported significantly higher emotional symptoms compared with the nontic group at both time points (Hoekstra et al., 2013). The tic group also demonstrated increased emotional symptoms at the second timepoint compared with the first, suggesting that internalizing emotional symptoms increase over time.

Association Between Anxiety and Tics

Anxiety and tics interact. In a study of 190 youth with TD, most non-OCD anxiety disorders were significantly more common in those with severe TD compared with mild/moderate TD (Coffey et al., 2000). Separation anxiety disorder was the strongest predictor of tic severity in this cohort. In addition, individuals with more types of anxiety disorders (e.g., diagnosed with both social phobia and separation anxiety disorder) tended to have a more severe tic phenotype (Coffey et al., 2000). In studies evaluating anxiety symptoms and tics dimensionally, there is a weak but positive association between anxiety and tic symptom severities (Marwitz and Pringsheim, 2018; Vermilion et al., 2021). These studies compared total anxiety symptom scores with tic severity scores. It is possible that a stronger association would be seen between specific anxiety symptoms and tics. For example, elevated separation anxiety symptom severity has been associated with significantly greater tic severity (Lewin et al., 2011).

The pathophysiological relationship between anxiety and tics is incompletely understood and likely complex. Increased anxiety may be associated with greater tic severity, but anxiety may also increase the negative effects that tics have on an individual's function. In a study of 500 adults with CTD, the strong association between tic severity and functional impairment was independently moderated by both anxiety and depressive symptoms (Lewin et al., 2011). This suggests that targeting tics alone may not be sufficient to improve function in individuals with co-occurring anxiety or depression. There is also likely an environmental contribution to the association between anxiety and tics. In a study of 45 youth with TD, Eaton et al. (2017) evaluated the impact of environmental consequences and internalizing symptoms on tic severity.

Environmental consequences were evaluated using the Tics Accommodation and Reaction Scale—Parent Report, which assesses consequences based on the setting and the type (e.g., escape). Youth with elevated social anxiety symptoms had more accommodations, such as being provided a break, in response to their tics. Youth with elevated separation anxiety symptoms had more overall consequences, particularly in public settings, in multiple domains. Although both anxiety symptoms and environmental consequences were associated with increased tic severity, environmental consequences most strongly predicted tic severity. Based on this model, it is possible that the association between anxiety and tics is mediated by accommodations or environmental consequences in response to tics.

Other studies suggest that the relationship between anxiety and tics is owing to impact of stress on tic suppression. Although tics are involuntary, they can be suppressed through cognitive mechanisms. In a small study of 10 participants, youth with CTD were exposed to a stress-inducing task and tic frequency and tic suppression were assessed (Conelea et al., 2011). Tic frequency did not increase but the ability to suppress tics was affected. In addition, in a study of finasteride for tic treatment, subjects reported that their tic reduction reflected an improvement in their ability to suppress tics (Bortolato et al., 2022). This suggests that stress may impact tics by inhibiting the ability to suppress tics voluntarily.

Anxiety and Premonitory Urge

The association between anxiety and tics may also be related to the premonitory urge. The premonitory urge is an unpleasant sensation that precedes the tic and may be relieved by performing the tic. The premonitory urge may be a focal sensation, often described as an “itch” or muscle tension, or a more generalized feeling of something being “not right.” This sensation is typically not described in younger children; urge onset is ∼3 years after tic onset (Leckman et al., 1993). It is not known if the premonitory urge is not yet present or if cognitive limitations in a younger population make it difficult to assess.

Anxiety may be linked to premonitory urge. Increased anxiety symptom severity has been associated with increased premonitory urge (Rozenman et al., 2015; Woods et al., 2005). There may be an overlap between the physical symptoms of anxiety and the sensory experience of the premonitory urge (Rozenman et al., 2015). In a sample of 124 youths with CTD who participated in the efficacy trial for a tic-specific behavioral therapy (Piacentini et al., 2010), baseline assessments of premonitory urge, anxiety, and tic severities were assessed (Rozenman et al., 2015). Premonitory urge severity, as measured by the validated self-report instrument Premonitory Urge in Tics Scale (PUTS) (Woods et al., 2005), positively correlated with tic severity (Rozenman et al., 2015). Individuals with elevated self-reported anxiety symptom severity had greater premonitory urge severity (Rozenman et al., 2015). Specifically, symptoms from the panic/somatic subscale, which the authors described as a modified physiologic arousal subscale, accounted for a large portion of variance in PUTS scores.

It is not known why or how anxiety symptoms, particularly somatic anxiety symptoms, and premonitory urge are related. However, one hypothesis is that alterations of interoceptive awareness contribute to the relationships among urge, anxiety, and tics (Ganos et al., 2015; Pile et al., 2018). Interoceptive awareness refers to one's ability to identify and respond to internal signals in the body, such as the urge to urinate. Studies evaluating interoception in CTD suggest that individuals with tics may process internal sensations differently from those without tics (Ganos et al., 2015; Pile et al., 2018). In a study of adults with CTD, increased interoceptive accuracy, as measured by heartbeat perception, was associated with increased premonitory urge severity (Ganos et al., 2015). However, the CTD group had overall lower interoceptive accuracy compared with the control group.

In a similar study carried out in youth with CTD, the CTD group had lower interoceptive accuracy but this was not associated with premonitory urge severity (Pile et al., 2018). The authors conclude that this discrepancy may be owing to age-related differences in the premonitory urge experience. Another study found that specific interoceptive components differed between individuals with tics and healthy controls (Narapareddy et al., 2022). Adults with CTD were found to have higher general awareness of bodily sensations and anxiety-associated somatization, although the anxiety-associated somatization was more closely associated with sex and OCD. In this study, the premonitory urge was found to be significantly associated with higher general body awareness (Narapareddy et al., 2022). Further investigations into the complex relationships among tics, anxiety, and interoception are warranted.

Tic Disorders and Stress Hormones

Corresponding with the differences in interoception, patients with tic disorders have shown sensory gating deficits and increased sensory over-responsivity (Isaacs and Riordan, 2020; Isaacs et al., 2022). Individuals with tic disorders have greater hypothalamic-pituitary-adrenal (HPA) axis activation in response to acute stress (Buse et al., 2014; Corbett et al., 2008; Godar and Bortolato, 2017; Leisman and Sheldon, 2022). This may result in an associated over-reaction to specific stimuli resulting in the premonitory urge or other unpleasant sensory phenomena (Godar and Bortolato, 2017). Triggers such as anxiety and frustration may compound stimuli, worsening the sensation of the premonitory urge (Godar and Bortolato, 2017).

It is thought that dopamine mediates the HPA response to acute stress and plays a role in the selection and inhibition of movements, with excess dopamine in the basal ganglia circuitry producing symptoms associated with tic disorders (Buse et al., 2014; Leckman et al., 2010; Leisman and Sheldon, 2022). Thus, tics may first occur as a result of cortical output and dopamine release in response to stressors, and then become a maladaptive coping mechanism (Godar and Bortolato, 2017). Supporting this idea, when cortisol rhythmicity was examined in a group of children with TD, they had higher cortisol levels in response to stress but lower evening cortisol, with a negative correlation between evening cortisol and tic severity (Corbett et al., 2008). This suggests an enhanced HPA axis response with tics possibly reflecting an anxiolytic effect to acute stress.

Animal studies have found that stress was associated with elevated levels of allopregnanolone in transgenic mice exhibiting tic-like behaviors (Bortolato et al., 2022; Mosher et al., 2017). Allopregnanolone was found to exacerbate tic-like responses in the setting of acute stress and decrease preimpulse inhibition, a marker for sensorimotor gating. Although the mechanism of allopregnanolone is unknown, one idea posits that the allopregnanolone decreases inhibition of the prefrontal cortex on the striatum, increasing dorsal striatal activity and inducing movement (Bortolato et al., 2022).

Brain Circuitry in Patients with TD

Although the exact mechanism of the relationship between anxiety and tics is not known, neural circuity studies suggest that interconnections exist between the basal ganglia-cerebellar-thalamo-cortical system, the HPA axis, the hippocampus, and the amygdala (Leisman and Sheldon, 2022). A hierarchy of information flow exists, which travels from the affective circuits to the motor circuits via the basal ganglia (Haber et al., 2000; Leisman and Sheldon, 2022). For example, the amygdala has direct connections with the striatum, which in turn has output to the motor system via the globus pallidus externa and interna and the substantia nigra pars reticulata (Leisman and Sheldon, 2022). In this way, the limbic system can affect emotional responses that could then result in increased motor output and tics. This corresponds with previous studies of circuits that suggest a rostral–caudal pathway from circuits associated with affective symptoms to those associated with simple motor tics, with disinhibition of thalamocortical circuits ultimately leading to tics (Albin and Mink, 2006; Mink, 2001).

The connection between emotions and tics is also supported by a functional magnetic resonance imaging (MRI) study in which limbic structures including the insula, amygdala, and anterior cingulate cortex activate 1 second before a tic (Neuner et al., 2014). In addition, there is a relationship between the right insula and the premonitory urge phenomenon (Draper et al., 2016; Jackson et al., 2021; Jackson et al., 2020; Tinaz et al., 2015), as well as different structural covariance networks in individuals with TD including, but not limited to, increased structural covariance of the right anterior-dorsal insula with the occipital cortex, cerebellum, and periaqueductal gray region and decreased structural covariance with the temporal lobe and right somatosensory cortex (Jackson et al., 2020).

Similarly, the cingulate cortex (particularly mid-cingulate cortex) has been shown to relate to the premonitory urge phenomena (Draper et al., 2016; Jackson et al., 2021) and has been found to have increased structural covariance with areas such as the bilateral motor cerebellum and inferior frontal cortex in patients with TD (Jackson et al., 2021). Although studies about structural connectivity of anxiety in individuals with tics are limited, one recent study used tractography to demonstrate that left insular to subthalamic nucleus connectivity positively correlated with anxiety scores, particularly in subjects with TD (Temiz et al., 2023). Thus, a neuroanatomic framework is established and studies have shown evidence of brain circuitry underlying the relationships among the limbic system, emotions, and tic disorders.

Anxiety Phenotype in CTD

Although anxiety disorders are common in CTD, it is not known whether the clinical features of anxiety symptoms in CTD are the same as anxiety symptoms in individuals without tics. In a sample of 176 youth with CTD not selected for co-occurring anxiety disorders, overall anxiety symptom severity was similar to the baseline anxiety symptom severity of 488 anxious treatment-seeking youth enrolled in the largest anxiety treatment trial to date, Child/Adolescent Anxiety Multimodal Study (CAMS), for which the study data are publicly available through the NIMH data archive (Vermilion et al., 2021). However, the specific anxiety phenotype seemed to differ between the two groups. Youth with CTD had significantly greater physical anxiety and separation anxiety symptom severities compared with the CAMS group. Social phobia symptom severities were similar (Vermilion et al., 2021).

The clinical course of anxiety symptoms may differ between youth with and without tic disorders. In nontic childhood anxiety disorders, separation anxiety improves with age, and social phobia becomes more prevalent (Kendall et al., 2016; Waite and Creswell, 2014; Weems and Costa, 2005). This age-related transition may not be present in youth with CTD (Vermilion et al., 2021). In the above study, there was no association between age and social phobia or separation anxiety symptom severities in the tic disorder group (Vermilion et al., 2021). In addition, when dividing the tic disorder group into children and adolescents, symptom severities in the social phobia and separation anxiety symptom domains did not differ between groups.

Similar to what has previously been published in pediatric anxiety, children in the CAMS group had significantly lower social phobia and significantly higher separation anxiety scores compared with adolescents in the CAMS group. Although longitudinal data are needed, these data suggest that social phobia symptoms may start earlier and separation anxiety symptoms may persist longer in youth with CTD.

Impact of Anxiety

Youth with anxiety and CTD consider a reduction of anxiety symptoms a high priority (Cuenca et al., 2015; Hollis et al., 2016). In interviews of young people with CTD, anxiety reduction was the second most desired outcome (after tic improvement) (Hollis et al., 2016). Of interest, although an anxiety disorder was reported in only 10% of participants, nearly half of participants identified wanting a treatment to manage negative emotions associated with tics. Several participants reported feeling anxious about their tics and that this anxiety fueled their tics. Participants also reported that negative emotions were more bothersome than the tics themselves. Indeed, anxiety is associated with impaired function in youth with tic disorders. In a study that assessed the impact of tic disorders on quality of life and family function in 193 youth, greater anxiety symptom severity was associated with worse child quality of life (Vermilion et al., 2020).

Eddy et al. (2011) also found that, in young people with TD, greater symptom severity of their co-occurring psychiatric conditions, including anxiety, were associated with worse quality of life. Similarly in adults with CTD, anxiety is related to worse overall and psychological health-related quality of life (Isaacs et al., 2022). The relationship between anxiety and negative functional impact may be age related. In a systematic literature review of quality of life across the lifespan in CTD, internalizing symptoms such as anxiety and depression had a stronger impact on quality of life in adults than children (Evans et al., 2016).

Treatment of Anxiety

Although reducing anxiety and negative emotions associated with tics is a priority in the CTD community (Cuenca et al., 2015), anxiety disorders may be undertreated in CTD (Specht et al., 2011). In a cohort of youth enrolled in the largest tic treatment trial to date (Piacentini et al., 2010), over one third of subjects had a non-OCD anxiety disorder (Specht et al., 2011). However, only 20% of these subjects reported taking a selective serotonin reuptake inhibitor (SSRI), which is the first-line pharmacologic treatment for pediatric anxiety disorders. It is possible that subjects with co-occurring anxiety disorders received psychotherapy or behavioral therapy instead of medication. It is also possible that anxiety symptoms were not severe enough to warrant treatment. However, these findings do raise concern that anxiety disorders may be underdiagnosed and/or undertreated in CTD.

When an individual with CTD presents with anxiety, clinicians treat anxiety symptoms in CTD as they would in individuals without tics. In pediatric anxiety disorders, pharmacotherapy, behavioral therapy, or a combination may be useful. In the CAMS trial, which evaluated the efficacy of sertraline, cognitive behavioral therapy (CBT), a combination, or placebo, combination treatment was superior to medication only, CBT only, and placebo (Walkup et al., 2008). Sertraline and CBT were superior to placebo but had similar efficacy to each other.

However, it is not clear what the best approach is to manage anxiety in CTD because it has not been specifically studied. It is possible that the approach to treatment of anxiety in tic disorders may differ from the general population. Because the phenotype of anxiety in CTD may differ (Vermilion et al., 2021), alternative treatment approaches may be warranted. There is evidence that other psychiatric conditions differ in CTD. For example, in tic-related OCD, the OCD phenotype differs from individuals without tics (de Vries et al., 2016; George et al., 1993; Holzer et al., 1994), and the presence of tics in OCD may moderate response to OCD treatment (Bloch et al., 2006; Masi et al., 2013; Skarphedinsson et al., 2015).

For individuals with treatment-resistant tics and anxiety, deep brain stimulation (DBS) may be a treatment option that could target both symptoms. Multiple studies have reported individuals with intractable TD treated with DBS have shown improvement in tic severity, anxiety severity, quality of life, and global functioning (Huys et al., 2016; Neudorfer et al., 2017; Porta et al., 2012). However, in some cases, DBS increased anxiety (Coulombe et al., 2018). Thus, more characterization of effects (both motor and psychiatric) related to DBS in a particular region is needed. DBS in pediatric populations remains controversial considering the limited evidence, the possibility of the tic disorder waning, and the risks associated with surgery (Coulombe et al., 2018; Tomskiy et al., 2022).

Yet, one must also consider that tics and associated psychiatric disorders can affect cognitive, emotional, and social development, as can the adverse effects of compounding medications (Tomskiy et al., 2022; Xu et al., 2020). Updated guidelines in 2015 removed a previously suggested 25-year-old age limit owing to these concerns (Schrock et al., 2015). DBS may be a treatment option for adolescents with severe and intractable TD who have been carefully assessed and selected for the procedure by a multidisciplinary team (Schrock et al., 2015; Xu et al., 2020).

Youth with CTD often have at least one co-occurring neuropsychiatric condition, and the presence of multiple neuropsychiatric conditions can make the approach to treatment challenging. Best practice guidelines recommend screening for co-occurring symptoms and first treating the most impairing symptom (Pringsheim et al., 2019). The presence of one diagnosis could affect how a patient responds to the treatment of another diagnosis. For example, in a study comparing a tic-specific behavior therapy (Comprehensive Behavioral Intervention for Tics; CBIT) to a psychoeducation control, tic severity reduction was less in those with a co-occurring anxiety disorder regardless of treatment arm (Sukhodolsky et al., 2017). Thus, it is possible that first treating anxiety will either decrease tic severity or improve response to subsequent tic treatment. However, the impact of treating anxiety has not been evaluated in CTD.

Future Directions

Anxiety disorders are common and can be impairing in youth with CTD. Yet, much work is still needed to understand the complex nature of these symptoms. Future research should focus on phenotyping anxiety in CTD, assessing the relationships among anxiety, tics, and other related symptoms, and managing anxiety in youth with CTD. Earlier estimates of anxiety prevalence in CTD focused on individuals meeting diagnostic criteria for specific anxiety disorders. This approach likely misses individuals with sub-threshold symptoms or symptom combinations that may still be impairing (Lewinsohn et al., 2004; Marwitz and Pringsheim, 2018; Rozenman et al., 2015; Safer et al., 2015). Indeed, the concept of framing anxiety as a spectrum disorder rather than as discrete categorical diagnoses is consistent with the NIMH-initiated Research Domain Criteria (RDoC) Framework (Insel et al., 2010). It is not known whether the clinical features of anxiety symptoms in CTD are the same as in anxiety disorders in nontic-affected individuals. Clear phenotyping of anxiety in CTD is an important initial step to designing therapeutic trials to target the impairing anxiety symptoms in CTD.

In addition to phenotyping anxiety in CTD, a better understanding of the relationships among tics, anxiety, and other co-occurring symptoms is necessary to understand approach to management of this complex neurodevelopmental disorder. Indeed, the close relationship between anxiety and tics suggests that management of one symptom may affect the other. However, treating tics first may not be effective in youth with co-occurring anxiety. Treatment of tics may not decrease co-occurring anxiety symptom severity (Woods et al., 2011), and the presence of an anxiety disorder may lessen the response to tic-specific treatment (Sukhodolsky et al., 2017). It is possible that treatment of anxiety symptoms first would improve tic severity or improve the subsequent response to a tic-specific intervention. Studies investigating this potential relationship are warranted.

Anxiety treatment studies in the CTD population are lacking but necessary. Indeed, as a strong contributor to functional impairment, improved treatment of anxiety in youth with CTD has high potential to improve functional outcomes.

Footnotes

Authors' Contributions

Y.S.: writing—original draft. J.V.: conceptualization, writing—reviewing and editing.

Disclosures

The authors declare no relevant disclosures or conflicts of interest.

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