Tic-Related Functional Impairment Drives the Relationship Between Tics and Depression in Youth With Tourette Syndrome

Abstract

Although many youth with Tourette syndrome (TS) have at least 1 comorbid psychiatric condition (eg, obsessive-compulsive disorder), the extent to which TS is associated with depression remains unclear. This cross-sectional study examined relationships among tic severity, tic-related functional impairment, and depressive symptoms in 277 youth with TS. Tic-related impairment, but not tic severity, was associated with both self- and parent-reported depressive symptoms. An age × sex interaction emerged, such that among younger participants, females reported higher depressive symptoms than males; however, this effect was observed only for self-report, not parent report. Additionally, both depressive symptoms and tic severity were associated with quality of life, though depressive symptoms accounted for substantially more variance. Overall, findings suggest that associations between tics and depression are modest and largely driven by impairment rather than tic severity per se. Depressive symptoms, however, significantly impact quality of life in youth with TS and warrant clinical attention.

Keywords

depression quality of life tics Tourette syndrome youth

Tourette syndrome (TS) is associated with functional impairment.¹ Youth with tics experience social difficulties such as embarrassment, exclusion, bullying,² discrimination,³ and problems in school,⁴ all of which can negatively impact quality of life⁵ and self-esteem.⁶ These difficulties are compounded by high rates of psychiatric comorbidities, such as attention-deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD).^7‐9 Although there is consistent evidence that tic disorders are associated with poorer quality of life,^1,10‐12 findings regarding their relationship with depression have been mixed. The present study aims to clarify the relationship between tic severity, tic-related functional impairment, and depressive symptoms in youth with TS, while accounting for relevant covariates.

Given the broad impact of tics on quality of life, researchers have investigated the relationship between tics and depression. Early cross-sectional work suggested that longer duration of tic symptoms in youth was associated with higher depression scores.¹³ Additional research found that adults with TS reported more severe depressive symptoms than healthy controls but did not differ from participants with a primary major depression diagnosis.¹⁴ A recent meta-analysis of 12 studies (samples were majority youth) estimated that 36.4% of individuals with tic disorders also have depression, with older age being associated with more severe depressive symptoms.¹⁵ Nonetheless, several of the studies included in this meta-analysis relied on self-report measures to approximate depression diagnoses, featured very small samples (as low as n = 22), demonstrated substantial heterogeneity in depression estimates, and drew from treatment-seeking populations. These methodologic limitations raise the possibility that reported depression rates may have been inflated.

Other research has not found robust relationships between tics and depression. Two studies found that depression symptoms did not correlate with tic severity, but instead moderated the relationship between tic severity and tic-related functional impairment.^16,17 Additional research found only a weak association between tic severity and depression symptoms in adults with TS (r = .29), and the authors estimated that the sample's depression T score was no greater than a reference sample representing the general population.¹⁸

Taken together, the relationship between tics and depression in individuals with tic disorders remains inconclusive, requiring further examination within large samples. Importantly, many individuals with tics experience minimal tic-related functional impairment. For example, among a sample of youth with TS referred to a treatment program, 88% met criteria for at least mild tics, but only 30% met criteria for tic-related functional impairment.¹⁹ This suggests that it may not be the presence of tics themselves but rather the degree of tic-related functional impairment that drives depression in individuals with TS. For example, a child with TS who experiences low self-esteem and difficulties with relationships because of their tics is likely at greater risk for depression than a youth with TS who perceives their tics as less of a barrier.

Another important factor to consider is the proposed direction of the relationship between tics and depression and how it is modeled. Prior studies have shown that depression predicts tic-related impairment in both youth¹⁷ and adults,¹⁶ and that depression can moderate the association between tic severity and impairment. However, we argue that tic-related functional impairment is better conceptualized as a predictor and depression as an outcome. Indeed, tics tend to emerge early in childhood between ages 5 and 9 years, and in many cases begin waning in the late teen or early adulthood years,²⁰ whereas first episodes of depression tend to arise in adolescence or early adulthood.²¹ Therefore, when depression is elevated among individuals with tics, it is more plausible that the chronicity or functional impact of tics contributes to depression rather than the reverse. This should be reflected in the way the relationship is modeled. Lastly, any association with depression likely depends on both gender and age. As noted, longer tic duration¹³ and older age¹⁵ have been shown to be positively associated with depressive symptoms. Although tic disorders are more common in boys,²² some research suggests that girls may exhibit greater tic severity.²³ It is also well established that girls have higher rates of depression than boys, particularly during adolescence.²⁴ Consideration of these factors is necessary for research on the relationship between tics and depressive symptoms.

Current Investigation

In the current study, we examined the relationships between tic severity, tic-related functional impairment, and depressive symptoms in a relatively large sample of youth (n = 277; ages 6-16) with TS. The primary goal was to determine which factors predicted unique variance in depression symptoms while controlling for age group and gender. Additionally, we explored the impact of anxiety disorder diagnosis on these relationships, as prior research has found higher rates of co-occurring anxiety than depression in tic disorders.¹⁸ We then explored the interaction of age group and gender in predicting depressive symptoms to determine which TS patients were most likely to report higher depressive symptoms. Finally, we examined whether tics have a unique association with quality of life when controlling for depressive symptoms. We examined both child self-report and parent report of depression symptoms to account for potential differences between informants.²⁵ Research has shown that parent reports of child depressive symptoms can be more predictive of later onset of mood disorders, particularly in younger children (ie, under 12 years).²⁶

Materials and Methods

Participants

A total of N = 277 youth with TS were recruited as part of 2 separate randomized clinical trials investigating the efficacy of deutetrabenazine for treating tics in this population (n = 158 from Coffey et al²⁷; n = 119 from Jankovic et al²⁸). Both studies had the same inclusion/exclusion criteria and baseline procedures, so the samples were pooled to increase statistical power for the present study. Inclusion criteria required participants to be 6-16 years of age, meet Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria for TS, and have a Total Tic Severity Score ≥20 on the Yale Global Tic Severity Scale (YGTSS).²⁹ See published trials for more detailed information about inclusion/exclusion criteria and recruitment.^27,28 Prior to study procedures, a parent or legal guardian for each participant provided informed consent, and when applicable, the participants themselves provided assent to participate. Both studies followed the Consolidated Standards of Reporting Trials (CONSORT) guidelines for randomized clinical trials.

Procedure

As part of the clinical trials, participants completed baseline measures of tic severity and impairment, depression, and quality of life, followed by 12 weeks of a randomized, double-blind, placebo-controlled trial of deutetrabenazine. The present study focused exclusively on the baseline measures.

Measures

Tic Severity and Impairment

The Yale Global Tic Severity Scale²⁹ was administered by trained interviewers to assess participants’ level of tic severity and associated functional impairment. The interview begins by listing all simple and complex motor and vocal tics experienced by the participant. The interviewer then works with the participant to rate the severity of their tics based on the following 5 criteria: number of tics, their frequency, intensity, complexity, and interference. Each domain is rated from 0 to 5. Tic severity for motor and vocal tics can each range from 0 to 25, with a combined Total Tic Severity (motor + vocal tics) ranging from 0 to 50. The interviewer then provides a single-item global rating of tic-related impairment, ranging from 0 to 50. Impairment ranges include none, minimal (“Tics associated with subtle difficulties in self-esteem, family life, social acceptance, or school or job functioning”), mild (“Tics associated with minor difficulties in…”), moderate (“…some clear problems in…”), marked (“…major difficulties…”), and severe (“…extreme difficulties…”). Internal consistency for total tic severity was good (α = .82); however, when Tic Impairment was added, internal consistency substantially worsened (α = .57). This suggested that tic severity and impairment operate as distinct but overlapping constructs, consistent with prior research.^30,31

Depression

Both participants and a parent completed the Children's Depression Inventory 2nd Edition (CDI-2).³² The CDI-2 presents 28 symptom items that are rated from 0 (absence of symptom) to 2 (definite symptom). Items yield a Total score and 2 subscales, emotional problems and functional problems. The aim of the present investigation was to examine the overall association between tics and depression, so the Total scores (self- and parent report, respectively) were used. Internal consistency was good for both self-(α = .83) and parent report (α = .84).

Quality of Life

The Gilles de la Tourette Syndrome–Quality of Life Scale for children and adolescents (CA-GTS-QOL) is a 27-item questionnaire assessing quality of life in children and adolescents living with TS.^33,34 Items are rated from 0 (no problem) to 4 (extreme problem) for a total score ranging from 0 to 108. Internal consistency was excellent (α = .90).

Data Analytic Plan

To examine the relationships between tic severity, tic-related functional impairment, and depressive symptoms, we ran bivariate correlations and conducted 2 linear regression models. In each model, tic severity and functional impairment served as the primary predictors, and depressive symptoms, assessed via self-report and parent report, served as the respective outcomes. In both models, we controlled for age group (6-11 years vs 12-16 years) and gender. In separate models, we also explored anxiety diagnosis as a binary covariate to determine its impact on these associations. To identify demographic subgroups of youth with TS who may be most likely to report elevated depressive symptoms, we also tested an age group by gender interaction term in each model. Lastly, to determine if tic severity or tic-related impairment had unique associations with quality of life, independent of depressive symptoms, we conducted 2 additional linear regression models. Self- and parent-reported depressive symptoms were included as covariates in their respective models.

Results

Descriptive Statistics

Most participants were boys (n = 223; 80.5%) and most were White (n = 237; 85.6%). The original trials stratified participants into 2 age groups: children (6-11 years) and adolescents (12-16 years). Overall, the mean age was 11.6 years (SD = 2.57) with 125 children (45.1%) and 152 adolescents (54.9%). Based on participant medical history, the most common psychiatric comorbidities were ADHD (39.35%), anxiety (14.44%), and OCD (13.72%). See Table 1 for sample demographics.

Table 1.

Sample Sociodemographic Characteristics.

Characteristic	n	%
Age group
6-11 y	125	45.10
12-16 y	152	54.90
Assigned sex at birth
Male	233	80.50
Female	44	19.50
Race
Asian	9	3.25
Black	7	2.53
Native American	5	1.81
White	237	85.60
Multiracial	6	2.17
Other	13	4.69
Ethnicity
Hispanic or Latino	45	16.25
Not Hispanic or Latino	226	81.59
Unknown	6	2.17
Psychiatric disorders
ADHD	109	39.35
OCD	38	13.72
Anxiety	40	14.44
Depression	15	5.42
Current medications
ADHD (stimulant and non-stimulant)	93	33.57
Antidepressant (SSRI or otherwise)	29	10.47

Abbreviations: ADHD, attention-deficit hyperactivity disorder; SSRI, selective serotonin reuptake inhibitor.

All variables met assumptions of normality based on indices of skewness and kurtosis, as well as visual inspection of histograms. Based on the YGTSS, both total tic severity and tic-related impairment fell in the moderate range. Additionally, CDI-2 scores suggested clinically significant depressive symptoms in the sample. Bivariate correlations indicated that parent-reported depressive symptoms were weakly associated with both higher tic severity (r = .13, P = .035) and tic-related impairment (r = .22, P < .001). On the other hand, self-reported depressive symptoms were weakly associated with only tic-related impairment (r = .20, P = .001) and not with tic severity (r = .11, P = .079). See Table 2 for descriptives and bivariate correlations.

Table 2.

Correlations Between Key Variables.

	Mean (SD)	1	2	3	4
1. Tic Severity	33.17 (6.32)
2. Tic Impairment	31.23 (8.47)	.54***
3. CDI-2 (Self-report)	26.00 (9.91)	.11	.20**
4. CDI-2 (Parent report)	30.01 (10.97)	.13*	.22***	.56***
5. QOL	33.58 (20.61)	.30***	.34***	.64***	.49***

Abbreviations: CDI-2, Children's Depression Inventory 2nd Edition; QOL, quality of life.

*P < .05; **P < .01; ***P < .001.

Predictors of Depressive Symptoms

In the first regression model, tic impairment predicted greater self-reported depression symptoms, but tic severity had no unique contribution. Neither gender nor age group predicted depressive symptoms. The overall model accounted for only 5% of the variance in depressive symptoms. The age group by gender interaction was added to the model and was statistically significant (B = 8.42, P = .005). Independent samples t tests indicated that within the children group (6-11), female participants (mean = 59.57, SD = 12.35) self-reported greater depressive symptoms than male participants (mean = 52.30, SD = 9.29), t(124) = 2.66, P = .013. In contrast, there were no gender differences within the adolescent age group, t(144) = –1.00, P = .321. See Table 3 for summary statistics and Figure 1 for the plotted interaction. This model was rerun with anxiety diagnosis included as a covariate. Anxiety status did not predict depression (B = 2.23, P = .229) and had no meaningful impact on the above findings.

Table 3.

Linear Regression With Sex, Age, Tic Severity and Tic Impairment as Predictors of Self- and Parent-Reported Depressive Symptoms.

	B	SE	sr ²	P value
Self-Reported^a
Male sex	−2.19	1.51	0.01	0.148
Age group	0.41	1.20	0.00	0.730
Total tic severity	0.00	0.12	0.00	0.974
Tic-related impairment	0.23	0.09	0.03	0.008
Parent-reported^b
Male sex	−0.11	1.64	0.00	0.645
Age group	1.05	1.31	0.00	0.879
Total tic severity	0.02	0.13	0.00	0.850
Tic-related impairment	0.28	0.09	0.03	0.003

Abbreviations: B, unstandardized beta; SE, standard error; sr² = semi-partial correlation.

F(4, 269) = 9.75, P = .014, R² = .05.

F(4, 269) = 3.69, P = .006, R² = .05.

In the second regression, again, only tic impairment significantly predicted parent-reported depressive symptoms, with no significant effects of gender, age group, or tic severity. Like the other model, this overall model also accounted for only 5% of the variance in parent-reported depressive symptoms. The age group by gender interaction was added to the model but was not statistically significant (B = 1.88, P = .569). See Table 3 for summary statistics. Again, anxiety status was added to the model as a covariate, but it was not associated with depressive symptoms (B = .862, P = .612) and did not meaningfully change any of the above findings.

Predictors of Quality of Life

In the first model, both self-reported depressive symptoms and tic severity predicted worse quality of life, but there was no effect of tic impairment. Similarly, in the second model, parent-reported depressive symptoms and tic severity predicted quality of life, but tic impairment did not. See Table 4 for summary statistics.

Table 4.

Linear Regression With Depressive Symptoms, Tic Severity, and Tic Impairment as Predictors of Quality of Life.

	B	SE	sr ²	P value
Depressive symptoms (self-report)^a	0.91	0.07	0.34	<.001
Total tic severity	0.41	0.13	0.02	0.002
Tic-related impairment	−0.18	0.20	0.00	0.380
Depressive symptoms (parent report)^b	0.60	0.07	0.18	<.001
Total tic severity	0.39	0.15	0.02	0.009
Tic-related impairment	−0.11	0.23	0.00	0.620

Abbreviations: B, unstandardized beta; SE, standard error; sr² = semi-partial correlation.

F(3, 266) = 79.11, P < .001, R² = .47.

F(3, 270) = 41.34, P < .001, R² = .32.

Discussion

Research examining risk for depression among youth with tic disorders has been mixed. The present study examined overall tic severity, tic-related functional impairment, demographic factors (age group and gender), and their associations with depressive symptoms in a large sample of youth with TS. Results indicated only a modest association between tics and depression, with effects primarily driven by tic-related functional impairment rather than tic severity itself. Additionally, all effects were unchanged by the inclusion of anxiety status as a covariate. These findings were consistent across both self- and parent-reported depressive symptoms. Additionally, younger girls with TS (ages 6-11) appeared to be at elevated risk for self-reported depressive symptoms. However, this interaction of age group and gender was not replicated in parent-reported depressive symptoms, suggesting potential informant discrepancies or developmental differences in the reporting of internalizing symptoms. Importantly, although tic severity was not associated with depressive symptoms, it was significantly associated with quality of life even after accounting for depression. Taken together, these findings suggest that while tics may meaningfully impact functioning and quality of life, they do not, in and of themselves, appear to be strongly associated with depression in youth with TS.

Although tic severity was not directly associated with depressive symptoms, tic-related functional impairment had consistent associations with depressive symptoms, suggesting that the consequences of tics—rather than their presence or intensity per se—may be more relevant to depression. One plausible explanation is that functional impairment, and subsequent depressive symptoms, are driven in part by environmental factors. For example, a child with TS who develops in a relatively supportive or tic-neutral environment may experience limited interference in functioning and maintain positive self-esteem and social relationships. In contrast, a child with similar tic severity who is exposed to bullying, criticism, or punitive responses may experience greater functional impairment, which could, in turn, increase vulnerability to depressive symptoms. Consistent with this perspective, prior research has demonstrated that environmental consequences of tics (eg, being told to stop expressing tics) are associated with increased tic severity and impairment³⁵ and greater internalizing symptoms, such as school anxiety and avoidance.³⁶ Moreover, Comprehensive Behavioral Intervention for Tics (CBIT), the first-line behavioral treatment, uses function-based interventions to identify the antecedents and consequences of a patient's tics to help them modify their environment to become more tic neutral.³⁷ Creating a tic-neutral environment reduces external reinforcers (eg, instructing individuals not to respond to tics), thereby reducing the patient's tics and associated functional impairment.³⁷ Taken together, environmental responses may play a critical role in shaping the functional impact of tics and, consequently, the risk for depression. Future research should directly examine environmental factors—such as family accommodation, peer responses, and school climate—as potential moderators of the relationship between tic-related impairment and depressive symptoms.

Interestingly, neither age group nor sex were independently associated with depressive symptoms in the present sample. This finding contrasts with prior research indicating that longer tic duration¹³ and older age¹⁵ are associated with greater depressive symptoms. For example, a recent meta-analysis of 12 samples spanning a wide age range (mean ages 6.75-33.75 years) reported a positive association between age and depression rates among individuals with tic disorders.¹⁵ One possible explanation for the absence of an age effect in the current study is that risk for depression may increase later in adolescence or adulthood—developmental periods not fully represented in the present sample. Similarly, sex differences in depression are typically most pronounced during late adolescence, with higher rates in females.³⁸ In contrast, the present findings indicated that higher depressive symptoms among females were observed only in the younger age group. This pattern diverges from expectations based on past research and may reflect developmental differences specific to youth with TS or sampling variability. Importantly, this effect was observed only for self-reported depressive symptoms and was not replicated in parent report, suggesting possible informant discrepancies when assessing internalizing symptoms. Taken together, these findings suggest that age and sex differences in depression among youth with TS may be more nuanced than previously thought and highlight the need for future research using broader age ranges and multi-informant designs to better understand these developmental patterns.

Despite the lack of a robust association between tic severity and depressive symptoms, greater tic severity was associated with poorer quality of life, even after accounting for depression. However, the size of this effect was small (approximately 2% of the variance) compared with the effect of depressive symptoms, which accounted for a substantially larger proportion of variance in quality of life (18%-34%, depending on informant). This pattern suggests that, although tic severity contributes to worse quality of life, the presence of depressive symptoms may have a bigger overall impact on functioning and well-being in youth with TS. Clinically, these findings underscore the importance of assessing and targeting depressive symptoms, even when tics are the primary presenting concern. In some cases when patients have comorbid TS and depression, it may be necessary to first address the depression before proceeding with CBIT for the tics. However, there is limited evidence that comorbidities reduce the overall efficacy of CBIT,³⁹ and additional research is needed to identify the optimal sequence for addressing comorbidities when a patient is seeking treatment for their tics.⁴⁰

Strengths of this study include the large sample of youth diagnosed with TS, the measurement of depression across informants (self- vs parent report), and the ability to statistically control for important demographic factors. Additionally, the study used validated assessment tools for both tic severity and depressive symptoms, enhancing the reliability and comparability of the findings. The inclusion of both self-reported and parent-reported outcomes allowed for a nuanced analysis of informant discrepancies, which is crucial for understanding internalizing symptoms in youth. Furthermore, the use of regression models to examine interactions between age group and gender provided valuable insights into developmental and demographic patterns in depression risk. The focus on quality of life as a distinct outcome, alongside depressive symptoms, also broadened the scope and clinical relevance of the research.

However, there are important limitations that should be considered. The analyses were cross-sectional, which limits the ability to draw conclusions about causality or the temporal sequence of relationships among tic severity, functional impairment, and depressive symptoms. Longitudinal research is needed to clarify whether tic-related impairment leads to depression, or whether the relationship is bidirectional. Additionally, because the sample was drawn from randomized controlled trials, inclusion/exclusion criteria required TS to be the primary presenting condition, with comorbidities—including depression—required to be secondary. This may have limited the range or variability of depressive symptoms in the sample and may impact the generalizability of the findings. The study sample was also relatively homogeneous, with >80% of participants identifying as White and a majority being male. The sample was also restricted to children and adolescents. These demographic limitations restrict the generalizability of the findings to more diverse populations, including those with different racial, ethnic, gender, and age backgrounds.

Conclusion

Although the majority of youth with TS present with at least 1 comorbid psychiatric condition, the present findings suggest that the relationship between tics and depression in this population is modest and is more strongly associated with tic-related functional impairment than with tic severity itself. In youth, tics may be more closely linked to conditions with shared neurobiologic etiologies, such as OCD, ADHD,⁹ and anxiety,¹⁸ rather than depression per se. Nevertheless, depressive symptoms were associated with significantly poorer quality of life, and their impact was greater than that of tic severity. Therefore, even if TS is not inherently related to elevated risk for depression, the presence of depressive symptoms has meaningful implications for functioning. These findings underscore the importance of assessing mood symptoms in youth presenting for TS treatment and suggest that addressing tic-related impairment and co-occurring depression may be essential for improving overall quality of life.

Footnotes

Acknowledgements

We would like to sincerely thank all authors and personnel involved in the original data collections on which this study is based (ie, Coffey et al, 2021; Jankovic et al, 2021).

ORCID iDs

Benjamin J. Mitchell

Erika S. Trent

Eric A. Storch

Ethical Considerations

The study protocols upon which this investigation is based were approved by national and local independent ethics committees or institutional review boards at each study site. The data were collected in accordance with the International Council for Harmonisation Good Clinical Practice Tripartite Guideline E6 and applicable national and local laws and regulations.

Consent to Participate

Prior to study procedures, a parent or legal guardian for each participant provided informed consent, and when applicable, the participants themselves provided assent to participate.

Author Contributions

Conceptualization: BJM, EIB, EST, SB, MFG, JS, EAS; Data curation: SB; Formal analysis: SB; Methodology: BJM, EIB, EST, SB, MFG, JS, EAS; Visualization: SB, BJM; Writing – original draft: BJM; Writing – review & editing: BJM, EIB, EST, SB, MFG, JS, EAS.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article:

Declaration of Conflicting Interests

The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Erika Trent receives research funding to her institution from the Texas Child Mental Health Care Consortium. Eric Storch reports receiving research funding to his institution from the Ream Foundation, International OCD Foundation, and the National Institutes of Health. He receives direct funding from the International OCD Foundation as well as MHNTI for providing trainings on treating obsessive-compulsive disorder with psychotherapy. He was a consultant for Brainsway and Biohaven Pharmaceuticals in the past 36 months. He owns stock options less than $5000 in NView (for distribution of the Y-BOCS and CY-BOCS) and receives royalties from OCD Scales LLC (for distribution of the Y-BOCS and CY-BOCS). He receives book royalties from Elsevier, Wiley, Oxford, American Psychological Association, Guildford, Springer, Routledge, and Jessica Kingsley. Steve Barash is an employee and shareholder of Teva Pharmaceuticals. Mark Gordon is a former employee and current shareholder of Teva Pharmaceuticals. Benjamin Mitchell, Emily Braley, and Jordan Stiede have no conflicts of interest or funding sources to disclose.

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