Challenging current diagnostic and classification criteria for primary tic disorders

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Sarna, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6135894/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Jun, 2025 Read the published version in European Child & Adolescent Psychiatry → Version 1 posted 9 You are reading this latest preprint version Abstract Background: Persistent motor and vocal tic disorders (PMTD/PVTD) are distinct diagnoses from Tourette syndrome (TS). In both, the threshold for the diagnosis is up to age 18, whereas tics infrequently manifest after age 12. Methods: In our cohort of youth with tic disorders from Calgary, Canada, we aimed to determine whether the clinical features and comorbidity profile of PMTD/PVTD differ from those of TS, and assess whether chronic tic disorders with adolescent-onset (age≥12) are different from disorders with childhood-onset (<12yr). Results: A total of 341 children and adolescents with primary chronic tic disorders were included (90.0% with TS, 7.0% with PMTD, 1.8% with PVTD). Regarding age at tic onset, participants with adolescent-onset tics (6.7%) were diagnosed with attention-deficit/hyperactivity disorder (ADHD) more often than those with childhood-onset (p=0.02); there were no differences in sex ratio, tic severity and impairment. Regarding tic disorder diagnosis, participants with PMTD/PVTD had a later age at tic onset than those with TS (p=0.01) and had less psychiatric comorbidity (p=0.01), specifically ADHD and obsessive-compulsive disorder; there were no differences in tic severity or impairment. Conclusions: Given that the major difference between TS and PMTD/PVTD lies in psychiatric comorbidities, which are not part of the diagnostic criteria, we suggest creating a single category for primary persistent tic disorders. Tic onset in adolescence is uncommon, and coupled with the lack of any major difference in clinical features, should lead us to question whether the age limit in the diagnostic criteria might not be more relevant as a supportive criterion. Gilles de la Tourette syndrome chronic motor or vocal tic disorder tics criteria adolescence attention deficit disorder with hyperactivity Figures Figure 1 Introduction According to the Fifth Edition of the Diagnostic and Statistical Manual (DSM) of Mental Disorders [ 1 ], Tourette syndrome (TS) is defined by the presence of at least two motor tics and at least one vocal tic, whereas persistent motor and vocal tic disorders (PMTD and PVTD) are defined by at least one of either motor or vocal tics. Tics must appear before the age of 18 years and last for more than a year, with other causes excluded. In a meta-analysis of population-based studies [ 2 ], the prevalence of PMTD was 1.65% (95%CI = 0.64–4.28), higher (but less precise) than that of TS at 0.77% (95%CI = 0.39–1.51), and that of PVTD at 0.69% (95%CI = 0.49–0.97). The largest study and meta-analysis comparing TS and PMTD/PVTD found that individuals with PMTD/PVTD may have a later age at tic onset, a lower tic severity and fewer psychiatric comorbidities compared to those with TS [ 3 ]. The authors suggested that these disorders are very similar, and may represent a single entity encompassing different levels of tic severity and impairment. The DSM-5 describes two other tic disorder diagnoses: ‘other specified tic disorder’ used when the person does not meet the criteria for a tic disorder and the clinician chooses to communicate the reason (e.g., age of onset is over 18 years), and ‘unspecified tic disorder’, used when the criteria for a tic disorder are not met and the clinician chooses not to specify the reason (e.g., there is insufficient information to make a more specific diagnosis). These labels are not frequently used clinically and may not reflect the reality of patients with tics. In the 2012 systematic review of the epidemiology of tic disorders, ‘pediatric tic disorder not otherwise specified’ reached a 0.79% prevalence (95%CI = 0.28–2.21, based on three studies), which is similar to the prevalence of TS [ 2 ]. Regarding age of onset, a different maximum age threshold has been used over the years to meet diagnostic criteria: it was first defined at 15 years in the DSM-III [ 4 ], then at 21 years in the DSM-III-TR, and eventually, it was modified to 18 years in the DSM-IV and remained here in the DSM-5 [ 1 ]. Looking at the natural history of tics, they typically begin around 6 years of age, worsen during early adolescence (age 10–12), and improve in late adolescence for a majority of patients [ 5 ]. In an international multisite study in 2000, it was found that 93% of 3500 individuals with TS (according to the DSM-III-R definition criteria) first developed tics before 10 years of age. Recently, a threshold of 12 years old was used to help differentiate patients with functional tic-like behaviours from patients with tics, with a specificity of 94% [ 6 ]. We used this 12-year threshold in our sample of youths with primary tics to determine if the presentation of adolescent-onset tics is different from childhood-onset tics (e.g. more severe or phenomenologically different, or if there are associations with more severe comorbidities). In 2024, a group of clinicians with expertise in tic disorders questioned the DSM-5 criteria [ 7 ], including age at symptom onset and the differentiation of tic disorder diagnoses, as others have done previously in 2010 [ 8 ]. They proposed a revision of diagnostic criteria for primary tic disorders. The aim of our study was to challenge the current classification criteria for primary tic disorders by 1) determining whether the clinical features and comorbidity profile of patients with PMTD/PVTD differ from those of patients with TS, and 2) assessing whether forms of chronic tic disorders first manifesting in adolescence (age 12 or older) are different from forms occurring in childhood (< 12 year) in our clinical registry. Methods Children and adolescents with primary tic disorders have been prospectively included in our Tic Disorder Registry at the Calgary Tourette and Pediatric Movement Disorder Clinic in Calgary, Canada, since 2017. Primary chronic tic disorders included TS, PMTD, PVTD, 'other specified tic disorder' and ‘unspecified tic disorder’, defined according to the diagnostic criteria of the DSM 5 [ 1 ]. We excluded from our study individuals with functional tic-like behaviours and individuals with provisional tic disorder. In this cross-sectional study, we recorded sex, age at first clinical assessment, age at tic onset, tics characteristics at the first clinical assessment, using the Yale Global Tic Severity Scale YGTSS (number of tics, severity of tics, and type of tics), the presence of mental health comorbidities (attention deficit/hyperactivity disorder [ADHD], obsessive compulsive disorder [OCD], anxiety and depression, autism spectrum disorder), and treatment. We compared these features between 1) children whose tics first started before 12 years of age (childhood onset) and youth whose tics started at 12 or older (adolescent onset), and 2) children and youth with TS, PMTD, and PVTD. In people who did not recall precise age at tic onset, they were asked if they thought it was during childhood, or adolescence. We excluded from our study individuals for which age at tic onset was totally unknown. We summarized data using means, 95%CI, and percentages, for the whole sample and for those participants aged 12 or older at inclusion, to determine if there were any substantial differences in phenomenology based on age. A Wilcoxon rank sum test was used to compare means when needed, and a chi2 test was used to compare categorical variables. All statistical analyses were performed using StataCorp. 2021. Stata Statistical Software: Release 17. College Station, TX: StataCorp LLC. This project received ethical approval from the University of Calgary Conjoint Health Research Ethics Board. Parents provided signed informed consent and children provided assent to study participation and publication of the study results. Results We excluded individuals with functional tic-like behaviours (n=53), individuals with provisional tic disorder (n=25) and individuals for which age at tic onset was totally unknown (n=2). One patient with a diagnosis of PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections) was also excluded since they did not meet criteria for a primary chronic tic disorder. A total of 341 children and adolescents with chronic tic disorders were therefore included, 77 females (22.6%) and 264 males (77.4%). Regarding tic disorder diagnosis, 307 (90.0%) had TS, 24 (7.0%) had PMTD, 6 (1.8%) had PVTD and 4 (1.2%) had an ‘other specified tic disorder’ because they had several phonic tics and only one motor tic, therefore not meeting criteria for TS, PMTD or PVTD. A total of 318 (93.3%) had a tic onset before 12 years old (see Figure 1); mean age at tic onset was 6.3 years (95%CI=6.0-6.6), and mean age at first visit was 10.7 years (95%CI=10.4-11.0). Regarding comorbidities, 172 (50.4%) had ADHD, 73 (21.4%) had OCD, 26 (7.6%) had depression, 101 (29.6%) had anxiety, and 34 (10%) had autism spectrum disorder. Only 75 (22.0%) had no psychiatric comorbidities (see Table 1). Table 1 Description and comparison of individuals according to childhood-onset (< 12 y) or adolescent-onset of tics (age 12 or older) Age of tic onset < 12 y N= 318 (93.3%) Age of at tic onset ≥ 12 y N= 23 (6.7%) Total N= 341 p Males, n (%) 247 (77.7%) 17 (73.9%) 264 (77.4%) 0.7 Age at tic onset, y N=311 5.8 (5.6-6.1) 12.8 (12.4-13.3) 6.3 (6.0-6.6) - Age at presentation, y 10.4 (10.1-10.7) 15.0 (14.5-15.4) 10.7 (10.4-11.0) - Latency tic onset-diagnosis, y N=311 4.6 (4.2-5.0) 2.1 (1.5-2.7) 4.4 (4.0-4.8) 0.001 Diagnosis, n (%) Tourette syndrome PMTD PVTD OSTD 289 (90.9%) 21 (6.6%) 5 (1.6%) 3 (0.9%) 18 (78.3%) 3 (13.0%) 1 (4.4%) 1 (4.4%) 307 (90.0%) 24 (7.0%) 6 (1.8%) 4 (1.2%) 0.2 Comorbidities, n (%) ADHD OCD Anxiety Depression None 155 (48.7%) 68 (21.4%) 92 (28.9%) 24 (7.6%) 72 (22.6%) 17 (73.9%) 5 (21.7%) 9 (39.1%) 2 (8.7%) 3 (13.0%) 172 (50.4%) 73 (21.4%) 101 (29.6%) 26 (7.6%) 75 (22%) 0.02 1.0 0.3 0.8 0.3 Number of tics Simple motor tics Simple vocal tics Complex motor tics Complex vocal tics 3.7 (3.4-3.9) 1.7 (1.5-1.9) 1.2 (1.0-1.5) 0.7 (0.5-0.8) 3.9 (2.8-5.1) 1.3 (0.7-1.9) 1.9 (0.9-2.8) 0.8 (0.3-1.4) 3.7 (3.4-3.9) 1.7 (1.5-1.9) 1.3 (1.1-1.5) 0.7 (0.5-0.8) 0.7 0.3 0.1 0.3 YGTSS Motor tic score Vocal tic score Total tic score Impairment score N=310 11.3 (10.8-11.8) 8.1 (7.5-8.7) 19.4 (18.4-20.3) 16.9 (15.5-18.4) 10.8 (8.4-13.1) 8.0 (5.6-10.5) 18.8 (15.2-22.4) 18.3 (12.2-24.3) 11.3 (10.8-11.8) 8.1 (7.5-8.7) 19.3 (18.4-20.2) 17.0 (15.6-18.4) 0.8 0.9 0.7 0.9 Treatment, n (%) Alpha agonists Neuroleptics SSRI Psychostimulants 83 (26.1%) 39 (12.3%) 44 (13.8%) 71 (22.3%) 5 (21.7%) 4 (17.4%) 5 (21.7%) 10 (43.5%) 88 (25.8%) 43 (12.6%) 49 (14.4%) 81 (23.8%) 0.8 0.2 0.3 0.02 Abbreviations: ADHD: attention deficit/ hyperactivity disorder, OCD: obsessive compulsive disorder, OSTD: other specified tic disorder, PMTD: persistent motor tic disorder, PVTD: persistent vocal tic disorders, SSRI: Selective Serotonin Reuptake Inhibitor, YGTSS: Yale Global Tic Severity Scale. Unless otherwise specified, numbers are means (95%CI). Presentation according to age at tic onset (childhood versus adolescent onset) We did not find differences between groups in sex ratio, tic disorder diagnosis, number of motor/phonic and simple/complex tics, or tic severity. Individuals with adolescent-onset tics had a shorter latency between tic onset and diagnosis than individuals with childhood-onset tics (2 years versus 4.5 years). We found a higher prevalence of ADHD in participants with adolescent onset, 74% versus 49% in those with childhood onset (p=0.02), and this was also visible in the use of psychostimulants (44% vs 22%, p=0.02). There was no other difference in comorbidity or treatment (see Table 1). Looking at tic phenomenology according to the YGTSS tic inventory, individuals in the adolescent-onset group had more complex arm movements (26% vs 11%, p=0.04), more complex head gestures (26% vs 9%, p=0.008), more simple hand movements (44% vs 23%, p=0.02), more clicking (17% vs 4%, p=0.02), and less humming (0% vs 15%, p=0.04). Presentation according to tic disorder diagnosis Participants with PMTD or PVTD had an overall later age at tic onset (7.5y, 95%CI=6.5-8.6) than participants with TS (6.2y, 95%CI=5.9-6.5, p=0.01). There was no significant difference in the sex ratio, age at clinical presentation or latency between tic onset and presentation at the clinic (see Table 2). Individuals with TS had more simple motor tics than participants with PMTD (3.9 vs 2.8, p=0.03); there were no differences in the number of complex motor tics or the severity of motor tics on the YGTSS. There were no differences in the number of vocal tics or the severity of vocal tics on the YGTSS between participants with TS and PVTD. Importantly, there was no difference in tic-related impairment between PMTD/PVTD participants and participants with TS. Looking at individual tics on the YGTSS tic inventory, participants with TS had more simple mouth movements than participants with PMTD (48% vs 25%, p=0.033) and this was the only phenomenological difference noted. Individuals with TS had more comorbid ADHD (52% vs 33%, p=0.05), and OCD (23% vs 7%, p=0.04) than individuals with PMTD/PVTD, without any difference in the use of pharmacological treatments. Overall, individuals with PMTD/PVTD had less psychiatric comorbidity (49% vs 20%, p=0.012). Table 2 Description and comparison of individuals according to the tic disorder diagnosis Persistent motor tic disorder N=24 (7.0%) Persistent vocal tic disorder N= 6 (1.8%) Persistent motor and vocal tic disorders N= 30 (8.8%) Tourette syndrome N= 307 (90.0%) p* Males, n (%) 20 (83.3%) 6 (100%) 26 (86.7%) 235 (76.6%) 0.2 Age at tic onset, y 7.3 (6.0-8.6) 8.3 (5.7-11.0) 7.5 (6.5-8.6) 6.2 (5.9-6.5) 0.01 Age at presentation, y 11.4 (10.2-12.6) 11.7 (10.0-13.4) 11.4 (10.5-12.4) 10.7 (10.3-11.0) 0.13 Individuals with a tic onset < 12yo, n (%) 21 (87.5%) 5 (83.3%) 26 (86.7%) 289 (94.1%) 0.11 Latency onset-diagnosis, y 4.7 (3.0-6.3) 3.3 (0.9-5.8) 4.4 (3.0-5.8) 4.6 (4.2-4.9) 0.8 Comorbidities , n (%) ADHD OCD Anxiety Depression No comorbidities 7 (29.2%) 2 (8.3%) 4 (16.7%) 1 (4.1%) 10 (41.7%) 3 (50%) 0 1 (16.7%) 0 2 (33.3%) 10 (33.3%) 2 (6.7%) 5 (16.7%) 1 (3.3%) 12 (49.0%) 160 (52.1%) 71 (23.1%) 94 (30.6%) 25 (8.1%) 62 (20.2%) 0.05 0.04 0.4 0.11 0.01 Treatment , n (%) Alpha agonists Neuroleptics SSRI Psychostimulants 4 (16.7%) 1 (4.2%) 2 (8.3%) 5 (20.8%) 1 (16.7%) 2 (33.3%) 2 (33.3%) 2 (33.3%) 5 (16.7%) 3 (10.0%) 4 (13.3%) 7 (23.3%) 80 (26.0%) 29 (12.7%) 44 (14.3%) 73 (23.8%) 0.5 0.2 0.9 1.0 Number of tics Simple motor tics Simple vocal tics Complex motor tics Complex vocal tics 2.8 (2.2-3.5) - 0.7 (0.2-1.2) - - 2 (1.1-2.9) - 0 3.9 (3.6-4.1) 1.8 (1.6-2.0) 1.4 (1.1-1.6) 0.7 (0.6-0.9) 0.03 0.4 0.2 0.09 YGTSS Motor tic score Vocal tic score Impairment score N= 23 10.3 (8.7-11.9) - 16.1 (11.4-20.7) N=6 - 10.2 (6.6-13.7) 11.7 (-8.7-32.0) - - 15.2 (10.3-20.0) N= 300 11.7 (11.2-12.1) 8.6 (8.0-9.2) 17.0 (15.5-18.5) 0.14 0.4 0.5 Abbreviations : ADHD: attention deficit/ hyperactivity disorder, OCD: obsessive compulsive disorder, SSRI: Selective Serotonin Reuptake Inhibitor, YGTSS: Yale Global Tic Severity Scale. *Comparison between PMTD/PVTD and TS, except for number of tics (comparison between PVTD and TS for phonic tics, and PMTD and TS for motor tics), excluding other specified tic disorders. Unless otherwise specified, numbers are means (95%CI). Discussion In our large sample of 341 children and adolescents with primary chronic tic disorders, we found only 10% of participants had diagnoses other than TS: 7.0% with PMTD, 1.8% with PVTD and 1.2% with an ‘other specified tic disorder’. The comorbidity burden was less in children with PMTD/PVTD, with few differences in tic severity or phenomenology. The main difference between participants with adolescent-onset tics and participants with childhood-onset tics was also concerning comorbidity, with a higher proportion of the adolescent group being diagnosed with ADHD, and no difference in tic severity and tic-related impairment. Presentation according to age at tic onset (childhood versus adolescent onset) Tics first appeared at the age of 12 or older in a small proportion of youth with TS in our study (6.7%), and in this group, there was no one with a tic onset at 16 years or older. This contrasts strikingly with the mean age of onset in functional tic-like behaviours, in the mid-teen years [9, 10]. This supports the recent suggestion of clinician experts [7] to use an upper age limit for tic onset as a supportive criterion for diagnosis, rather than a mandatory one, and to set this age limit at 12 years. As a parallel, in the few descriptions of idiopathic adult-onset tics (after the age of 18), they appear to be similar in phenomenology to childhood-onset tics, with variations in severity, even when they are not a recurrence of childhood tics [11,12]. The shorter delay between tic onset and first specialist consultation for tics of adolescent onset may be due to greater healthcare seeking tendencies among teenagers. This could be related to higher social awareness in teenagers when it comes to unvoluntary movements and sounds, or greater insight and recognition of premonitory urges compared to younger children. There were minor differences in phenomenology and somatic distribution of tics between participants with childhood onset and adolescent onset, but it is difficult to draw any conclusions due to the overall small number of participants with adolescent onset. These differences do not seem to be clinically significant, especially since there was no difference in tic severity and impairment, the main feature when considering treatment. Most importantly, participants with adolescent-onset tics had a higher prevalence of diagnosed ADHD than participants with childhood-onset tics (p=0.02). It cannot be excluded that adolescents and their parents reporting a tic onset after the age of 12 have overlooked the appearance of tics before that age, or inaccurately recalled age at onset, whilst ADHD was overshadowing tic symptoms. While ADHD is usually diagnosed in early school age years (mean age at diagnosis: 7.0 years, 95%CI=6.9-7.2) [13], it is possible that the higher prevalence of ADHD in our adolescent onset population is related to the longer period of time available to receive this diagnosis, or unmasking of tics related to psychostimulant use. Future studies could examine in this subgroup the severity of ADHD symptoms and that of other comorbidities. Presentation according to tic disorder diagnosis Children and adolescents with PMTD/PVTD represented only 9% of our sample of youth with chronic tic disorders. They did not differ from those with TS in terms of sex ratio, unlike in the larger study and meta-analysis by Claudio‐Campos et al[3] showing that individuals with PMTD/PVTD were more likely to be females. In our sample, children with PMTD/PVTD had a later age at tic onset than those with TS, which was suggested in some prior work [3, 13]. This could be related to comorbidity: tics are often diagnosed when patients come to medical attention due to coexisting psychiatric symptoms; if they tend to have less psychiatric symptoms, they might be diagnosed with tics later. In our work, there were almost no differences in tic severity in the two groups (when considering motor and vocal tics distinctly), nor in phenomenology of tics, whereas previous work suggests otherwise. In a study aiming to explore the expression of tics in OCD patients, Diniz et al [14] found that participants with OCD and TS presented higher tic severity scores than did patients with OCD and PMTD/PVTD. In 2019, Muller Vahl et al explored differences between 40 individuals with PMTD and 978 with TS and found that people with PMTD had a lower mean tic severity (Shapiro Tourette-Syndrome Severity Scale Global Severity Ratings=2.03, SD=0.86, vs. 2.83, SD=1.17; p < 0.001), even after controlling for age [15]. It is important to remember that the Shapiro Tourette-Syndrome Severity Scale does not assess separately motor and phonic tics, which could influence the analysis of tic severity. In the same study, individuals with TS had more often complex motor tics (55.9% vs 27.5%; p<0.01), copropraxia (16.2% vs 0%; p<0.01) and echopraxia (23.8% vs 10.0%; p<0.05) [15]. In the Claudio-Campos et al’s meta-analysis [3], individuals with PMTD/PVTD also had lower tic severity compared to individuals with TS (e.g. mean difference in YGTSS motor tic severity in two cohorts = −5.30, p<0.001; difference in YGTSS vocal tic severity in one cohort: −8.10, p<0.001). These studies did not look at tic-related impairment. In our sample, there was no difference in tic-related impairment, the latter being the main concern when considering treatment. We therefore question whether maintaining a distinction in classification between PMTD/PVTD and TS is relevant to patients. This is all the more true since phonic tics are simply considered by many as ‘motor tics that involve oral, nasal, pharyngeal, laryngeal and respiratory musculature’ leading to sounds [16]. The most striking difference and the one that has been consistently reported in the literature is the difference in the comorbidity profile: individuals with PMTD/PVTD from our sample had less psychiatric comorbidity than individuals with TS (49% vs 20%, p=0.012), specifically less ADHD and OCD. It should be noted that there were no significantly more adolescent-onset cases among participants with PMTD or PVTD compared to among participants with TS. In 1995, Spencer et al [17] compared 32 children with TS and 39 children with chronic tics, who only differed in rates of OCD, oppositional defiant disorder, and simple phobia (higher rates in TS). In the Claudio Campos’ meta-analysis of 11 datasets [3], the odds of comorbid OCD and ADHD were both more than 50% lower in PMTD/PVTD compared with TS, without significant differences in mood and anxiety disorders. In the Müller-Vahl et al’s study, individuals with PMTD/PVTD had a markedly lower comorbidity score (1.9 vs. 2.7; p < 0.001) as compared to TS patients [15]. Previous authors suggested that TS and PMTD/PVTD are part of the same clinical spectrum with different levels of severity, PMTD/PVTD being milder forms. Our findings suggest that this is mainly driven by the severity of the comorbidities and not by tic severity. However, psychiatric comorbidity has been associated with increased tic severity [18-21]. Current and prior work show that both groups of individuals with PMTD/PVTD or TS are not treated differently. Moreover, these disorders seem to rely on the same genetic causes [22] and pathophysiological mechanisms [23]. An interesting result was the 1.2% prevalence of ‘other specified tic disorder’ in our cohort, which was similar to the one of PVTD (1.8%). In our opinion, this term encompasses a poorly described group of individuals in the literature and adds to a complex labeling. Limitations Limitations of our work include our monocentric design, and the relatively small number of individuals with PMTD/PVTD and of adolescent-onset. It is likely that some individuals do not remember precisely the age of onset of tics, or that they were simply not aware of them at a young age, leading us to suspect that an even smaller proportion than that observed in our sample actually had an age of onset of tics of 12 years or more. Additionally, one may criticize our choice of 12 years old to compare age at tic onset in youth. This was motivated by a desire to separate the pre/per-pubertal and post-pubertal period, and to use a threshold similar to that used in functional tic-like behaviours, so as to contrast their differences. Furthermore, we do not have the proportions of individuals who declined to participate in the Registry; it is possible that parents of children with higher number or severity of comorbidities may be more motivated to participate in research, which can influence our data. Finally, children and adolescents were included from a tertiary referral centre, therefore children with mild tics are less likely to belong to the Registry. The same is true for PMTD, PVTD and TS, therefore we do not expect this particular bias to influence our results. Conclusion Given that the major difference between TS and PMTD/PVTD relies on psychiatric comorbidities, which are not required for the diagnosis of the condition, we suggest making a single category for primary persistent tic disorders. This does not lessen the importance of associated symptoms for patients, which should be assessed and treated in the context of this complex neurodevelopmental disorder. Simplifying labeling may help affected individuals, their families and health-care providers by improving their understanding and acceptance of this condition. The uncommon onset of tics after the age of 12, and similarly in adulthood, and the absence of major clinical differences questions if the age limit in the diagnostic criteria would be more relevant as a supportive criterion. In a previously mentioned work, Müller-Vahl et al proposed a new term for primary tic disorders, “tic spectrum disorders” [15]. We support efforts underway to find a global term which the scientific and patient communities agree on and accurately reflects the condition [24]. Declarations Conflict of interest: none. Funding or competing interests: No funding was received for conducting this study. Financial interests : Christelle Nilles has received research grants from the French Gilles de la Tourette Association in 2021 and in 2024. Davide Martino has received consulting honoraria from Ipsen Canada and AbbVie, lecturing honoraria from the Movement Disorders Society and the Canadian Movement Disorders Society, royalties from Oxford University Press, and research grant support from the Weston Family Foundation and the Canadian Institutes of Health Research. Julian Fletcher has no financial interests. Justyna Sarna has received consulting honoraria from AbbVie. Tamara Pringsheim has received research grant support from the Canadian Institutes of Health Research, and the Azrieli Accelerator of the University of Calgary Non-financial interests: Christelle Nilles is an unpaid member of the Board of the European Society for the Study of Tourette syndrome (ESSTS). Ethics approval This project received ethical approval from the University of Calgary Conjoint Health Research Ethics Board. Parents provided signed informed consent and children provided assent to study participation and publication of the study results. Authors’ contribution statements. All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Christelle Nilles and Tamara Pringsheim. The first draft of the manuscript was written by Christelle Nilles and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. References American Psychiatric Association (2013) Diagnostic and Statistical Manual of Mental Disorders, 5th edn. In: American Psychiatric Publishing, Washington, DC Knight T, Steeves T, Day L, Lowerison M, Jette N, Pringsheim T (2012) Prevalence of Tic Disorders: A Systematic Review and Meta-Analysis. Pediatr Neurol 47:77–90. https://doi.org/10.1016/j.pediatrneurol.2012.05.002 Claudio-Campos K, Stevens D, Koo S, Valko A, Bienvenu OJ, Budman CB, Cath DC, Darrow S, Geller D, Goes FS, Grados MA, Greenberg BD, Greenberg E, Hirschtritt ME, Illmann C, Ivankovic F, King RA, Knowles JA, Krasnow J, Lee PC, Lyon GJ, McCracken JT, Robertson MM, Osiecki L, Riddle MA, Rouleau G, Sandor P, Nestadt G, Samuels J, Scharf JM, Mathews CA, TAAICG) and the OCD Collaborative Genetics Association Study (OCGAS) (2021) Is Persistent Motor or Vocal Tic Disorder a Milder Form of Tourette Syndrome? Mov Disord 36:1899–1910. https://doi.org/10.1002/mds.28593 . for the Tourette Association of America International Consortium for Genetics American Psychiatric Association (1980) Diagnostic and Statistical Manual of Mental Disorders. Washington DC Freeman RD, Fast DK, Burd L, Kerbeshian J, Robertson MM, Sandor P (2000) An international perspective on Tourette syndrome: selected findings from 3500 individuals in 22 countries. Dev Med Child Neurol 42:436–447. https://doi.org/10.1017/S0012162200000839 Nilles C, Martino D, Pringsheim T (2024) Testing the specificity of phenomenological criteria for functional tic-like behaviours in youth with Tourette syndrome. Euro J Neurol e16262. https://doi.org/10.1111/ene.16262 Sarchioto M, Frey J, Ganos C, Gilbert DL, Hartmann A, Hedderly T, Isaacs D, Malaty I, Martindale JM, Medina Escobar A, Müller-Vahl KR, Okun MS, Parnes M, Sarva H, Śmilowska K, Szejko N, Tomczak K, Worbe Y, Pringsheim T, Martino D, Movement Disorders Society (2024) the Tic Disorders Study Group of the International Parkinson’s and Diagnostic Criteria for Primary Tic Disorders: Time for Reappraisal. Movement Disorders 39:1276–1281. https://doi.org/10.1002/mds.29868 Walkup JT, Ferrão Y, Leckman JF, Stein DJ, Singer H (2010) Tic disorders: some key issues for DSM-V. Depress Anxiety 27:600–610. https://doi.org/10.1002/da.20711 Martino D, Hedderly T, Murphy T, Müller-Vahl KR, Dale RC, Gilbert DL, Rizzo R, Hartmann A, Nagy P, Anheim M, Owen T, Malik O, Duncan M, Heyman I, Liang H, McWilliams A, O’Dwyer S, Fremer C, Szejko N, Han VX, Kozlowska K, Pringsheim TM (2023) The spectrum of functional tic‐like behaviours: Data from an international registry. Euro J Neurol 30:334–343. https://doi.org/10.1111/ene.15611 Pringsheim T, Ganos C, Nilles C, Cavanna AE, Gilbert DL, Greenburg E, Hartmann A, Hedderly T, Heyman I, Liang H, Malaty I, Malik O, Debes NM, Vahl KM, Munchau A, Murphy T, Nagy P, Owen T, Rizzo R, Skov L, Stern J, Szejko N, Worbe Y, Martino D (2023) The ESSTS (European Society for the Study of Tourette Syndrome) 2022 Criteria for Clinical Diagnosis of Functional Tic Like Behaviours (FTLBs): An international consensus from experts in tic disorders. Euro J of Neurology ene.15672. https://doi.org/10.1111/ene.15672 Chouinard S, Ford B (2000) Adult onset tic disorders. J Neurol Neurosurg Psychiatry 68:738–743. https://doi.org/10.1136/jnnp.68.6.738 Robakis D (2017) How Much Do We Know about Adult-onset Primary Tics? Prevalence, Epidemiology, and Clinical Features. Tremor Other Hyperkinet Mov (N Y) 7:441. https://doi.org/10.7916/D8SQ95ND Visser SN, Danielson ML, Bitsko RH, Holbrook JR, Kogan MD, Ghandour RM, Perou R, Blumberg SJ (2014) Trends in the Parent-Report of Health Care Provider-Diagnosed and Medicated Attention-Deficit/Hyperactivity Disorder: United States, 2003–2011. J Am Acad Child Adolesc Psychiatry 53:34–46e2. https://doi.org/10.1016/j.jaac.2013.09.001 Diniz JB, Rosario-Campos MC, Hounie AG, Curi M, Shavitt RG, Lopes AC, Miguel EC (2006) Chronic tics and Tourette syndrome in patients with obsessive–compulsive disorder. J Psychiatr Res 40:487–493. https://doi.org/10.1016/j.jpsychires.2005.09.002 Müller-Vahl KR, Sambrani T, Jakubovski E (2019) Tic disorders revisited: introduction of the term tic spectrum disorders. Eur Child Adolesc Psychiatry 28:1129–1135. https://doi.org/10.1007/s00787-018-01272-7 Robertson MM, Eapen V, Singer HS, Martino D, Scharf JM, Paschou P, Roessner V, Woods DW, Hariz M, Mathews CA, Črnčec R, Leckman JF (2017) Gilles de la Tourette syndrome. Nat Rev Dis Primers 3:16097. https://doi.org/10.1038/nrdp.2016.97 Spencer T, Biederman J, Harding M, Wilens T, Faraone S (1995) The Relationship between Tic Disorders and Tourette’s Syndrome Revisited. J Am Acad Child Adolesc Psychiatry 34:1133–1139. https://doi.org/10.1097/00004583-199509000-00009 Marwitz L, Pringsheim T (2018) Clinical Utility of Screening for Anxiety and Depression in Children with Tourette Syndrome. J Can Acad Child Adolesc Psychiatry 27:15–21 Pringsheim T (2017) Tic Severity and Treatment in Children: The Effect of Comorbid Attention Deficit Hyperactivity Disorder and Obsessive Compulsive Behaviors. Child Psychiatry Hum Dev 48:960–966. https://doi.org/10.1007/s10578-017-0718-z Rizzo R, Gulisano M, Martino D, Robertson MM (2017) Gilles de la Tourette Syndrome, Depression, Depressive Illness, and Correlates in a Child and Adolescent Population. J Child Adolesc Psychopharmacol 27:243–249. https://doi.org/10.1089/cap.2016.0120 Lewin AB, Storch EA, Conelea CA, Woods DW, Zinner SH, Budman CL, Scahill LD, Compton SN, Walkup JT, Murphy TK (2011) The roles of anxiety and depression in connecting tic severity and functional impairment. J Anxiety Disord 25:164–168. https://doi.org/10.1016/j.janxdis.2010.08.016 Yu D, Sul JH, Tsetsos F, Nawaz MS, Huang AY, Zelaya I, Illmann C, Osiecki L, Darrow SM, Hirschtritt ME, Greenberg E, Muller-Vahl KR, Stuhrmann M, Dion Y, Rouleau G, Aschauer H, Stamenkovic M, Schlögelhofer M, Sandor P, Barr CL, Grados M, Singer HS, Nöthen MM, Hebebrand J, Hinney A, King RA, Fernandez TV, Barta C, Tarnok Z, Nagy P, Depienne C, Worbe Y, Hartmann A, Budman CL, Rizzo R, Lyon GJ, McMahon WM, Batterson JR, Cath DC, Malaty IA, Okun MS, Berlin C, Woods DW, Lee PC, Jankovic J, Robertson MM, Gilbert DL, Brown LW, Coffey BJ, Dietrich A, Hoekstra PJ, Kuperman S, Zinner SH, Luðvigsson P, Sæmundsen E, Thorarensen Ó, Atzmon G, Barzilai N, Wagner M, Moessner R, Ophoff R, Pato CN, Pato MT, Knowles JA, Roffman JL, Smoller JW, Buckner RL, Willsey AJ, Tischfield JA, Heiman GA, Stefansson H, Stefansson K, Posthuma D, Cox NJ, Pauls DL, Freimer NB, Neale BM, Davis LK, Paschou P, Coppola G, Mathews CA, Scharf JM on behalf of the Tourette Association of America International Consortium for Genetics, the Gilles de la Tourette GWAS Replication Initiative, the Tourette International Collaborative Genetics Study, and the Psychiatric Genomics Consortium Tourette Syndrome Working Group (2019) Interrogating the Genetic Determinants of Tourette’s Syndrome and Other Tic Disorders Through Genome-Wide Association Studies. AJP 176:217–227. https://doi.org/10.1176/appi.ajp.2018.18070857 Martino D, Ganos C, Worbe Y (2018) Neuroimaging Applications in Tourette’s Syndrome. International Review of Neurobiology. Elsevier, pp 65–108 Tammy H (2024) Tic-Talk: Voices on Tourette Labelling. https://www.essts.org/news/tic-talk-voices-on-tourette-labelling Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 18 Jun, 2025 Read the published version in European Child & Adolescent Psychiatry → Version 1 posted Editorial decision: Revision requested 13 Apr, 2025 Reviews received at journal 08 Apr, 2025 Reviews received at journal 07 Apr, 2025 Reviewers agreed at journal 05 Apr, 2025 Reviewers agreed at journal 05 Apr, 2025 Reviewers invited by journal 15 Mar, 2025 Editor assigned by journal 05 Mar, 2025 Submission checks completed at journal 05 Mar, 2025 First submitted to journal 01 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6135894","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":425068142,"identity":"d26e700b-8778-4e50-8e81-7918a83c5863","order_by":0,"name":"Christelle Nilles","email":"","orcid":"","institution":"Hôpital Fondation Rothschild","correspondingAuthor":false,"prefix":"","firstName":"Christelle","middleName":"","lastName":"Nilles","suffix":""},{"id":425068143,"identity":"dd083697-5d2c-4ca3-a526-f212d66b716c","order_by":1,"name":"Davide Martino","email":"","orcid":"","institution":"University of Calgary","correspondingAuthor":false,"prefix":"","firstName":"Davide","middleName":"","lastName":"Martino","suffix":""},{"id":425068144,"identity":"ae60f60b-9ea0-4a58-ae5a-d180c433dbf1","order_by":2,"name":"Julian Fletcher","email":"","orcid":"","institution":"University of Calgary","correspondingAuthor":false,"prefix":"","firstName":"Julian","middleName":"","lastName":"Fletcher","suffix":""},{"id":425068145,"identity":"320eab25-6794-42a5-8f1b-bff620e8d246","order_by":3,"name":"Justyna R. Sarna","email":"","orcid":"","institution":"University of Calgary","correspondingAuthor":false,"prefix":"","firstName":"Justyna","middleName":"R.","lastName":"Sarna","suffix":""},{"id":425068146,"identity":"6490f753-2962-40c5-a689-85324c347716","order_by":4,"name":"Tamara Pringsheim","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABQ0lEQVRIiWNgGAWjYFADZiBmbGDgYWBvALIKcCvkwdTCcwDIMiBGCwNECwODRAJ+LfbspxM/V9Qw5Jm38x5++XOHjYzuzDeGH34Y1Mqbz0hg/PADiy08uZslzxxjKJY5zJdmzXsmjcfsdo6xZI/BccM5NxKYJXuwOSx3g2QDG0PiDGYeM2PGtsMgLWYMPAbHGGdIJLChORyihf/t5p8N/yBaDH+2/ecxu3nGjPGPwTF7kBbGP1i0SORuk2xsA2sxfsDbdoDH7AaPGTOPQU0iSAszNltuvN1m2dgnUSwBtIWZty2Zx+xMWrG0jMGB5Bk8D5ulZTC1sPfnbr7Z8M0mT4L/jPHHn2129mbHD2/8+KaiznYGe/LBj29whjU4LtgkkEQOMzAIJDbg1AAEIC3MH5AE6hgY+A/g0zEKRsEoGAUjBwAAMLpi+k97PTMAAAAASUVORK5CYII=","orcid":"","institution":"University of Calgary","correspondingAuthor":true,"prefix":"","firstName":"Tamara","middleName":"","lastName":"Pringsheim","suffix":""}],"badges":[],"createdAt":"2025-03-01 17:08:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6135894/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6135894/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00787-025-02732-7","type":"published","date":"2025-06-18T15:57:10+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":78238516,"identity":"d996545c-5eba-462f-8223-bdf2a000057e","added_by":"auto","created_at":"2025-03-11 08:45:03","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":171848,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of age at tic onset in the sample of children and adolescent with chronic tic disorders (n=341).\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6135894/v1/72a1e6d5e753f15baec6e44f.jpeg"},{"id":85231310,"identity":"b68c837a-acac-4611-b3e4-77f6a6468f1c","added_by":"auto","created_at":"2025-06-23 16:05:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":994789,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6135894/v1/25d116a1-8ad6-4295-b75f-54705bfd6cfe.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Challenging current diagnostic and classification criteria for primary tic disorders","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAccording to the Fifth Edition of the Diagnostic and Statistical Manual (DSM) of Mental Disorders [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], Tourette syndrome (TS) is defined by the presence of at least two motor tics and at least one vocal tic, whereas persistent motor and vocal tic disorders (PMTD and PVTD) are defined by at least one of either motor or vocal tics. Tics must appear before the age of 18 years and last for more than a year, with other causes excluded. In a meta-analysis of population-based studies [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], the prevalence of PMTD was 1.65% (95%CI\u0026thinsp;=\u0026thinsp;0.64\u0026ndash;4.28), higher (but less precise) than that of TS at 0.77% (95%CI\u0026thinsp;=\u0026thinsp;0.39\u0026ndash;1.51), and that of PVTD at 0.69% (95%CI\u0026thinsp;=\u0026thinsp;0.49\u0026ndash;0.97). The largest study and meta-analysis comparing TS and PMTD/PVTD found that individuals with PMTD/PVTD may have a later age at tic onset, a lower tic severity and fewer psychiatric comorbidities compared to those with TS [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The authors suggested that these disorders are very similar, and may represent a single entity encompassing different levels of tic severity and impairment.\u003c/p\u003e \u003cp\u003eThe DSM-5 describes two other tic disorder diagnoses: \u0026lsquo;other specified tic disorder\u0026rsquo; used when the person does not meet the criteria for a tic disorder and the clinician chooses to communicate the reason (e.g., age of onset is over 18 years), and \u0026lsquo;unspecified tic disorder\u0026rsquo;, used when the criteria for a tic disorder are not met and the clinician chooses not to specify the reason (e.g., there is insufficient information to make a more specific diagnosis). These labels are not frequently used clinically and may not reflect the reality of patients with tics. In the 2012 systematic review of the epidemiology of tic disorders, \u0026lsquo;pediatric tic disorder not otherwise specified\u0026rsquo; reached a 0.79% prevalence (95%CI\u0026thinsp;=\u0026thinsp;0.28\u0026ndash;2.21, based on three studies), which is similar to the prevalence of TS [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRegarding age of onset, a different maximum age threshold has been used over the years to meet diagnostic criteria: it was first defined at 15 years in the DSM-III [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], then at 21 years in the DSM-III-TR, and eventually, it was modified to 18 years in the DSM-IV and remained here in the DSM-5 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Looking at the natural history of tics, they typically begin around 6 years of age, worsen during early adolescence (age 10\u0026ndash;12), and improve in late adolescence for a majority of patients [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. In an international multisite study in 2000, it was found that 93% of 3500 individuals with TS (according to the DSM-III-R definition criteria) first developed tics before 10 years of age. Recently, a threshold of 12 years old was used to help differentiate patients with functional tic-like behaviours from patients with tics, with a specificity of 94% [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. We used this 12-year threshold in our sample of youths with primary tics to determine if the presentation of adolescent-onset tics is different from childhood-onset tics (e.g. more severe or phenomenologically different, or if there are associations with more severe comorbidities).\u003c/p\u003e \u003cp\u003eIn 2024, a group of clinicians with expertise in tic disorders questioned the DSM-5 criteria [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], including age at symptom onset and the differentiation of tic disorder diagnoses, as others have done previously in 2010 [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. They proposed a revision of diagnostic criteria for primary tic disorders. The aim of our study was to challenge the current classification criteria for primary tic disorders by 1) determining whether the clinical features and comorbidity profile of patients with PMTD/PVTD differ from those of patients with TS, and 2) assessing whether forms of chronic tic disorders first manifesting in adolescence (age 12 or older) are different from forms occurring in childhood (\u0026lt;\u0026thinsp;12\u0026nbsp;year) in our clinical registry.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eChildren and adolescents with primary tic disorders have been prospectively included in our Tic Disorder Registry at the Calgary Tourette and Pediatric Movement Disorder Clinic in Calgary, Canada, since 2017. Primary chronic tic disorders included TS, PMTD, PVTD, 'other specified tic disorder' and \u0026lsquo;unspecified tic disorder\u0026rsquo;, defined according to the diagnostic criteria of the DSM 5 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. We excluded from our study individuals with functional tic-like behaviours and individuals with provisional tic disorder.\u003c/p\u003e \u003cp\u003eIn this cross-sectional study, we recorded sex, age at first clinical assessment, age at tic onset, tics characteristics at the first clinical assessment, using the Yale Global Tic Severity Scale YGTSS (number of tics, severity of tics, and type of tics), the presence of mental health comorbidities (attention deficit/hyperactivity disorder [ADHD], obsessive compulsive disorder [OCD], anxiety and depression, autism spectrum disorder), and treatment. We compared these features between 1) children whose tics first started before 12 years of age (childhood onset) and youth whose tics started at 12 or older (adolescent onset), and 2) children and youth with TS, PMTD, and PVTD. In people who did not recall precise age at tic onset, they were asked if they thought it was during childhood, or adolescence. We excluded from our study individuals for which age at tic onset was totally unknown.\u003c/p\u003e \u003cp\u003eWe summarized data using means, 95%CI, and percentages, for the whole sample and for those participants aged 12 or older at inclusion, to determine if there were any substantial differences in phenomenology based on age. A Wilcoxon rank sum test was used to compare means when needed, and a chi2 test was used to compare categorical variables. All statistical analyses were performed using StataCorp. 2021. \u003cem\u003eStata Statistical Software: Release 17.\u003c/em\u003e College Station, TX: StataCorp LLC.\u003c/p\u003e \u003cp\u003e This project received ethical approval from the University of Calgary Conjoint Health Research Ethics Board. Parents provided signed informed consent and children provided assent to study participation and publication of the study results.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eWe excluded individuals with functional tic-like behaviours (n=53), individuals with provisional tic disorder (n=25) and individuals for which age at tic onset was totally unknown (n=2). One patient with a diagnosis of PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections) was also excluded since they did not meet criteria for a primary chronic tic disorder.\u003c/p\u003e\n\u003cp\u003eA total of 341 children and adolescents with chronic tic disorders were therefore included, 77 females (22.6%) and 264 males (77.4%). Regarding tic disorder diagnosis, 307 (90.0%) had TS, 24 (7.0%) had PMTD, 6 (1.8%) had PVTD and 4 (1.2%) had an \u0026lsquo;other specified tic disorder\u0026rsquo; because they had several phonic tics and only one motor tic, therefore not meeting criteria for TS, PMTD or PVTD. A total of 318 (93.3%) had a tic onset before 12 years old (see Figure 1); mean age at tic onset was 6.3 years (95%CI=6.0-6.6), and mean age at first visit was 10.7 years (95%CI=10.4-11.0). Regarding comorbidities, 172 (50.4%) had ADHD, 73 (21.4%) had OCD, 26 (7.6%) had depression, 101 (29.6%) had anxiety, and 34 (10%) had autism spectrum disorder. Only 75 (22.0%) had no psychiatric comorbidities (see Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1\u0026nbsp;\u003c/strong\u003eDescription and comparison of individuals according to childhood-onset (\u0026lt; 12 y) or adolescent-onset of tics (age 12 or older)\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"588\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3605%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.4082%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge of tic onset \u0026lt; 12 y\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eN= 318 (93.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.4082%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge of at tic onset \u0026ge; 12 y\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eN= 23 (6.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.4082%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eN= 341\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.415%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3605%;\"\u003e\n \u003cp\u003eMales, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.4082%;\"\u003e\n \u003cp\u003e247 (77.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.4082%;\"\u003e\n \u003cp\u003e17 (73.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.4082%;\"\u003e\n \u003cp\u003e264 (77.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.415%;\"\u003e\n \u003cp\u003e0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3605%;\"\u003e\n \u003cp\u003eAge at tic onset, y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.4082%;\"\u003e\n \u003cp\u003eN=311\u003c/p\u003e\n \u003cp\u003e5.8 (5.6-6.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.4082%;\"\u003e\n \u003cp\u003e12.8 (12.4-13.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.4082%;\"\u003e\n \u003cp\u003e6.3 (6.0-6.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.415%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3605%;\"\u003e\n \u003cp\u003eAge at presentation, y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.4082%;\"\u003e\n \u003cp\u003e10.4 (10.1-10.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.4082%;\"\u003e\n \u003cp\u003e15.0 (14.5-15.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.4082%;\"\u003e\n \u003cp\u003e10.7 (10.4-11.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.415%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3605%;\"\u003e\n \u003cp\u003eLatency tic onset-diagnosis, y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.4082%;\"\u003e\n \u003cp\u003eN=311\u003c/p\u003e\n \u003cp\u003e4.6 (4.2-5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.4082%;\"\u003e\n \u003cp\u003e\u0026nbsp;2.1 (1.5-2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.4082%;\"\u003e\n \u003cp\u003e\u0026nbsp;4.4 (4.0-4.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.415%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3605%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiagnosis, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eTourette syndrome\u003c/p\u003e\n \u003cp\u003ePMTD\u003c/p\u003e\n \u003cp\u003ePVTD\u003c/p\u003e\n \u003cp\u003eOSTD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.4082%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e289 (90.9%)\u003c/p\u003e\n \u003cp\u003e21 (6.6%)\u003c/p\u003e\n \u003cp\u003e5 (1.6%)\u003c/p\u003e\n \u003cp\u003e3 (0.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.4082%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e18 (78.3%)\u003c/p\u003e\n \u003cp\u003e3 (13.0%)\u003c/p\u003e\n \u003cp\u003e1 (4.4%)\u003c/p\u003e\n \u003cp\u003e1 (4.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.4082%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e307 (90.0%)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e24 (7.0%)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6 (1.8%)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.415%;\"\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3605%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eComorbidities, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eADHD\u003c/p\u003e\n \u003cp\u003eOCD\u003c/p\u003e\n \u003cp\u003eAnxiety\u003c/p\u003e\n \u003cp\u003eDepression\u003c/p\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.4082%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e155 (48.7%)\u003c/p\u003e\n \u003cp\u003e68 (21.4%)\u003c/p\u003e\n \u003cp\u003e92 (28.9%)\u003c/p\u003e\n \u003cp\u003e24 (7.6%)\u003c/p\u003e\n \u003cp\u003e72 (22.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.4082%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e17 (73.9%)\u003c/p\u003e\n \u003cp\u003e5 (21.7%)\u003c/p\u003e\n \u003cp\u003e9 (39.1%)\u003c/p\u003e\n \u003cp\u003e2 (8.7%)\u003c/p\u003e\n \u003cp\u003e3 (13.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.4082%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e172 (50.4%)\u003c/p\u003e\n \u003cp\u003e73 (21.4%)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e101 (29.6%)\u003c/p\u003e\n \u003cp\u003e26 (7.6%)\u003c/p\u003e\n \u003cp\u003e75 (22%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.415%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.02\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003cp\u003e0.3\u003c/p\u003e\n \u003cp\u003e0.8\u003c/p\u003e\n \u003cp\u003e0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3605%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber of tics\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eSimple motor tics\u003c/p\u003e\n \u003cp\u003eSimple vocal tics\u003c/p\u003e\n \u003cp\u003eComplex motor tics\u003c/p\u003e\n \u003cp\u003eComplex vocal tics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.4082%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3.7 (3.4-3.9)\u003c/p\u003e\n \u003cp\u003e1.7 (1.5-1.9)\u003c/p\u003e\n \u003cp\u003e1.2 (1.0-1.5)\u003c/p\u003e\n \u003cp\u003e0.7 (0.5-0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.4082%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3.9 (2.8-5.1)\u003c/p\u003e\n \u003cp\u003e1.3 (0.7-1.9)\u003c/p\u003e\n \u003cp\u003e1.9 (0.9-2.8)\u003c/p\u003e\n \u003cp\u003e0.8 (0.3-1.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.4082%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3.7 (3.4-3.9)\u003c/p\u003e\n \u003cp\u003e1.7 (1.5-1.9)\u003c/p\u003e\n \u003cp\u003e1.3 (1.1-1.5)\u003c/p\u003e\n \u003cp\u003e0.7 (0.5-0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.415%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.7 \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.3 \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.1 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.3 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3605%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eYGTSS\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMotor tic score\u003c/p\u003e\n \u003cp\u003eVocal tic score\u003c/p\u003e\n \u003cp\u003eTotal tic score\u003c/p\u003e\n \u003cp\u003eImpairment score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.4082%;\"\u003e\n \u003cp\u003eN=310\u003c/p\u003e\n \u003cp\u003e11.3 (10.8-11.8)\u003c/p\u003e\n \u003cp\u003e8.1 (7.5-8.7)\u003c/p\u003e\n \u003cp\u003e19.4 (18.4-20.3)\u003c/p\u003e\n \u003cp\u003e16.9 (15.5-18.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.4082%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e10.8 (8.4-13.1)\u003c/p\u003e\n \u003cp\u003e8.0 (5.6-10.5)\u003c/p\u003e\n \u003cp\u003e18.8 (15.2-22.4)\u003c/p\u003e\n \u003cp\u003e18.3 (12.2-24.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.4082%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e11.3 (10.8-11.8)\u003c/p\u003e\n \u003cp\u003e8.1 (7.5-8.7)\u003c/p\u003e\n \u003cp\u003e19.3 (18.4-20.2)\u003c/p\u003e\n \u003cp\u003e17.0 (15.6-18.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.415%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.8 \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.9\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.7 \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.9 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 26.3605%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eAlpha agonists\u003c/p\u003e\n \u003cp\u003eNeuroleptics\u003c/p\u003e\n \u003cp\u003eSSRI\u003c/p\u003e\n \u003cp\u003ePsychostimulants\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.4082%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e83 (26.1%)\u003c/p\u003e\n \u003cp\u003e39 (12.3%)\u003c/p\u003e\n \u003cp\u003e44 (13.8%)\u003c/p\u003e\n \u003cp\u003e71 (22.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.4082%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5 (21.7%)\u003c/p\u003e\n \u003cp\u003e4 (17.4%)\u003c/p\u003e\n \u003cp\u003e5 (21.7%)\u003c/p\u003e\n \u003cp\u003e10 (43.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.4082%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e88 (25.8%)\u003c/p\u003e\n \u003cp\u003e43 (12.6%)\u003c/p\u003e\n \u003cp\u003e49 (14.4%)\u003c/p\u003e\n \u003cp\u003e81 (23.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.415%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.8\u003c/p\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003cp\u003e0.3\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.02\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e ADHD: attention deficit/ hyperactivity disorder, OCD: obsessive compulsive disorder, OSTD: other specified tic disorder, PMTD: persistent motor tic disorder, PVTD: persistent vocal tic disorders, SSRI: Selective Serotonin Reuptake Inhibitor, YGTSS: Yale Global Tic Severity Scale.\u003c/p\u003e\n\u003cp\u003eUnless otherwise specified, numbers are means (95%CI).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePresentation according to age at tic onset (childhood versus adolescent onset)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe did not find differences between groups in sex ratio, tic disorder diagnosis, number of motor/phonic and simple/complex tics, or tic severity. Individuals with adolescent-onset tics had a shorter latency between tic onset and diagnosis than individuals with childhood-onset tics (2 years versus 4.5 years). We found a higher prevalence of ADHD in participants with adolescent onset, 74% versus 49% in those with childhood onset (p=0.02), and this was also visible in the use of psychostimulants (44% vs 22%, p=0.02). There was no other difference in comorbidity or treatment (see Table 1).\u003c/p\u003e\n\u003cp\u003eLooking at tic phenomenology according to the YGTSS tic inventory, individuals in the adolescent-onset group had more complex arm movements (26% vs 11%, p=0.04), more complex head gestures (26% vs 9%, p=0.008), more simple hand movements (44% vs 23%, p=0.02), more clicking (17% vs 4%, p=0.02), and less humming (0% vs 15%, p=0.04).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePresentation according to tic disorder diagnosis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants with PMTD or PVTD had an overall later age at tic onset (7.5y, 95%CI=6.5-8.6) than participants with TS (6.2y, 95%CI=5.9-6.5, p=0.01). There was no significant difference in the sex ratio, age at clinical presentation or latency between tic onset and presentation at the clinic (see Table 2).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIndividuals with TS had more simple motor tics than participants with PMTD (3.9 vs 2.8, p=0.03); there were no differences in the number of complex motor tics or the severity of motor tics on the YGTSS. There were no differences in the number of vocal tics or the severity of vocal tics on the YGTSS between participants with TS and PVTD. Importantly, there was no difference in tic-related impairment between PMTD/PVTD participants and participants with TS.\u003c/p\u003e\n\u003cp\u003eLooking at individual tics on the YGTSS tic inventory, participants with TS had more simple mouth movements than participants with PMTD (48% vs 25%, p=0.033) and this was the only phenomenological difference noted.\u003c/p\u003e\n\u003cp\u003eIndividuals with TS had more comorbid ADHD (52% vs 33%, p=0.05), and OCD (23% vs 7%, p=0.04) than individuals with PMTD/PVTD, without any difference in the use of pharmacological treatments. Overall, individuals with PMTD/PVTD had less psychiatric comorbidity (49% vs 20%, p=0.012).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2 Description and comparison of individuals according to the tic disorder diagnosis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"623\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.1878%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.175%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePersistent motor tic disorder\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eN=24 (7.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3355%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePersistent vocal tic disorder\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eN= 6 (1.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3355%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePersistent motor and vocal tic disorders\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eN= 30 (8.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.2616%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTourette syndrome\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eN= 307 (90.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.70465%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep*\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.1878%;\"\u003e\n \u003cp\u003eMales, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.175%;\"\u003e\n \u003cp\u003e20 (83.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3355%;\"\u003e\n \u003cp\u003e6 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3355%;\"\u003e\n \u003cp\u003e26 (86.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.2616%;\"\u003e\n \u003cp\u003e235 (76.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.70465%;\"\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.1878%;\"\u003e\n \u003cp\u003eAge at tic onset, y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.175%;\"\u003e\n \u003cp\u003e7.3 (6.0-8.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3355%;\"\u003e\n \u003cp\u003e8.3 (5.7-11.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3355%;\"\u003e\n \u003cp\u003e7.5 (6.5-8.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.2616%;\"\u003e\n \u003cp\u003e6.2 (5.9-6.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.70465%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.1878%;\"\u003e\n \u003cp\u003eAge at presentation, y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.175%;\"\u003e\n \u003cp\u003e11.4 (10.2-12.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3355%;\"\u003e\n \u003cp\u003e11.7 (10.0-13.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3355%;\"\u003e\n \u003cp\u003e11.4 (10.5-12.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.2616%;\"\u003e\n \u003cp\u003e10.7 (10.3-11.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.70465%;\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.1878%;\"\u003e\n \u003cp\u003eIndividuals with a tic onset \u0026lt; 12yo, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.175%;\"\u003e\n \u003cp\u003e21 (87.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3355%;\"\u003e\n \u003cp\u003e5 (83.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3355%;\"\u003e\n \u003cp\u003e26 (86.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.2616%;\"\u003e\n \u003cp\u003e289 (94.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.70465%;\"\u003e\n \u003cp\u003e0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.1878%;\"\u003e\n \u003cp\u003eLatency onset-diagnosis, y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.175%;\"\u003e\n \u003cp\u003e\u0026nbsp;4.7 (3.0-6.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3355%;\"\u003e\n \u003cp\u003e3.3 (0.9-5.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3355%;\"\u003e\n \u003cp\u003e4.4 (3.0-5.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.2616%;\"\u003e\n \u003cp\u003e4.6 (4.2-4.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.70465%;\"\u003e\n \u003cp\u003e0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.1878%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eComorbidities\u003c/strong\u003e, n (%)\u003c/p\u003e\n \u003cp\u003eADHD\u003c/p\u003e\n \u003cp\u003eOCD\u003c/p\u003e\n \u003cp\u003eAnxiety\u003c/p\u003e\n \u003cp\u003eDepression\u003c/p\u003e\n \u003cp\u003eNo comorbidities\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.175%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7 (29.2%)\u003c/p\u003e\n \u003cp\u003e2 (8.3%)\u003c/p\u003e\n \u003cp\u003e4 (16.7%)\u003c/p\u003e\n \u003cp\u003e1 (4.1%)\u003c/p\u003e\n \u003cp\u003e10 (41.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3355%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (50%)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e1 (16.7%)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e2 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3355%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e10 (33.3%)\u003c/p\u003e\n \u003cp\u003e2 (6.7%)\u003c/p\u003e\n \u003cp\u003e5 (16.7%)\u003c/p\u003e\n \u003cp\u003e1 (3.3%)\u003c/p\u003e\n \u003cp\u003e12 (49.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.2616%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e160 (52.1%)\u003c/p\u003e\n \u003cp\u003e71 (23.1%)\u003c/p\u003e\n \u003cp\u003e94 (30.6%)\u003c/p\u003e\n \u003cp\u003e25 (8.1%)\u003c/p\u003e\n \u003cp\u003e62 (20.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.70465%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.04\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003cp\u003e0.11\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.1878%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment\u003c/strong\u003e, n (%)\u003c/p\u003e\n \u003cp\u003eAlpha agonists\u003c/p\u003e\n \u003cp\u003eNeuroleptics\u003c/p\u003e\n \u003cp\u003eSSRI\u003c/p\u003e\n \u003cp\u003ePsychostimulants\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.175%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (16.7%)\u003c/p\u003e\n \u003cp\u003e1 (4.2%)\u003c/p\u003e\n \u003cp\u003e2 (8.3%)\u003c/p\u003e\n \u003cp\u003e5 (20.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3355%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1 (16.7%)\u003c/p\u003e\n \u003cp\u003e2 (33.3%)\u003c/p\u003e\n \u003cp\u003e2 (33.3%)\u003c/p\u003e\n \u003cp\u003e2 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3355%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5 (16.7%)\u003c/p\u003e\n \u003cp\u003e3 (10.0%)\u003c/p\u003e\n \u003cp\u003e4 (13.3%)\u003c/p\u003e\n \u003cp\u003e7 (23.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.2616%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e80 (26.0%)\u003c/p\u003e\n \u003cp\u003e29 (12.7%)\u003c/p\u003e\n \u003cp\u003e44 (14.3%)\u003c/p\u003e\n \u003cp\u003e73 (23.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.70465%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003cp\u003e0.9\u003c/p\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.1878%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber of tics\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eSimple motor tics\u003c/p\u003e\n \u003cp\u003eSimple vocal tics\u003c/p\u003e\n \u003cp\u003eComplex motor tics\u003c/p\u003e\n \u003cp\u003eComplex vocal tics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.175%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2.8 (2.2-3.5)\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e0.7 (0.2-1.2)\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3355%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e2 (1.1-2.9)\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3355%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.2616%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3.9 (3.6-4.1)\u003c/p\u003e\n \u003cp\u003e1.8 (1.6-2.0)\u003c/p\u003e\n \u003cp\u003e1.4 (1.1-1.6)\u003c/p\u003e\n \u003cp\u003e0.7 (0.6-0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.70465%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.03\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.1878%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eYGTSS\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMotor tic score\u003c/p\u003e\n \u003cp\u003eVocal tic score\u003c/p\u003e\n \u003cp\u003eImpairment score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.175%;\"\u003e\n \u003cp\u003eN= 23\u003c/p\u003e\n \u003cp\u003e10.3 (8.7-11.9)\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e16.1 (11.4-20.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3355%;\"\u003e\n \u003cp\u003eN=6\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e10.2 (6.6-13.7)\u003c/p\u003e\n \u003cp\u003e11.7 (-8.7-32.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.3355%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e15.2 (10.3-20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.2616%;\"\u003e\n \u003cp\u003eN= 300\u003c/p\u003e\n \u003cp\u003e11.7 (11.2-12.1)\u003c/p\u003e\n \u003cp\u003e8.6 (8.0-9.2)\u003c/p\u003e\n \u003cp\u003e17.0 (15.5-18.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.70465%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations\u003c/strong\u003e: ADHD: attention deficit/ hyperactivity disorder, OCD: obsessive compulsive disorder, SSRI: Selective Serotonin Reuptake Inhibitor, YGTSS: Yale Global Tic Severity Scale.\u003c/p\u003e\n\u003cp\u003e*Comparison between PMTD/PVTD and TS, except for number of tics (comparison between PVTD and TS for phonic tics, and PMTD and TS for motor tics), excluding other specified tic disorders.\u003c/p\u003e\n\u003cp\u003eUnless otherwise specified, numbers are means (95%CI).\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn our large sample of 341 children and adolescents with primary chronic tic disorders, we found only 10% of participants had diagnoses other than TS: 7.0% with PMTD, 1.8% with PVTD and 1.2% with an ‘other specified tic disorder’. The comorbidity burden was less in children with PMTD/PVTD, with few differences in tic severity or phenomenology. The main difference between participants with adolescent-onset tics and participants with childhood-onset tics was also concerning comorbidity, with a higher proportion of the adolescent group being diagnosed with ADHD, and no difference in tic severity and tic-related impairment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePresentation according to age at tic onset (childhood versus adolescent onset)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTics first appeared at the age of 12 or older in a small proportion of youth with TS in our study (6.7%), and in this group, there was no one with a tic onset at 16 years or older. This contrasts strikingly with the mean age of onset in functional tic-like behaviours, in the mid-teen years [9, 10]. This supports the recent suggestion of clinician experts [7] to use an upper age limit for tic onset as a supportive criterion for diagnosis, rather than a mandatory one, and to set this age limit at 12 years. As a parallel, in the few descriptions of idiopathic adult-onset tics (after the age of 18), they appear to be similar in phenomenology to childhood-onset tics, with variations in severity, even when they are not a recurrence of childhood tics [11,12].\u003c/p\u003e\n\u003cp\u003eThe shorter delay between tic onset and first specialist consultation for tics of adolescent onset may be due to greater healthcare seeking tendencies among teenagers. This could be related to higher social awareness in teenagers when it comes to unvoluntary movements and sounds, or greater insight and recognition of premonitory urges compared to younger children. There were minor differences in phenomenology and somatic distribution of tics between participants with childhood onset and adolescent onset, but it is difficult to draw any conclusions due to the overall small number of participants with adolescent onset. These differences do not seem to be clinically significant, especially since there was no difference in tic severity and impairment, the main feature when considering treatment.\u003c/p\u003e\n\u003cp\u003eMost importantly, participants with adolescent-onset tics had a higher prevalence of diagnosed ADHD than participants with childhood-onset tics (p=0.02). It cannot be excluded that adolescents and their parents reporting a tic onset after the age of 12 have overlooked the appearance of tics before that age, or inaccurately recalled age at onset, whilst ADHD was overshadowing tic symptoms. While ADHD is usually diagnosed in early school age years (mean age at diagnosis: 7.0 years, 95%CI=6.9-7.2) [13], it is possible that the higher prevalence of ADHD in our adolescent onset population is related to the longer period of time available to receive this diagnosis, or unmasking of tics related to psychostimulant use. Future studies could examine in this subgroup the severity of ADHD symptoms and that of other comorbidities.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePresentation according to tic disorder diagnosis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eChildren and adolescents with PMTD/PVTD represented only 9% of our sample of youth with chronic tic disorders. They did not differ from those with TS in terms of sex ratio, unlike in the larger study and meta-analysis by Claudio‐Campos et al[3] showing that individuals with PMTD/PVTD were more likely to be females. In our sample, children with PMTD/PVTD had a later age at tic onset than those with TS, which was suggested in some prior work [3, 13]. This could be related to comorbidity: tics are often diagnosed when patients come to medical attention due to coexisting psychiatric symptoms; if they tend to have less psychiatric symptoms, they might be diagnosed with tics later.\u003c/p\u003e\n\u003cp\u003eIn our work, there were almost no differences in tic severity in the two groups (when considering motor and vocal tics distinctly), nor in phenomenology of tics, whereas previous work suggests otherwise. In a study aiming to explore the expression of tics in OCD patients, Diniz et al [14] found that participants with OCD and TS presented higher tic severity scores than did patients with OCD and PMTD/PVTD. In 2019, Muller Vahl et al explored differences between 40 individuals with PMTD and 978 with TS and found that people with PMTD had a lower mean tic severity (Shapiro Tourette-Syndrome Severity Scale Global Severity Ratings=2.03, SD=0.86, vs. 2.83, SD=1.17; p \u0026lt; 0.001), even after controlling for age [15]. It is important to remember that the Shapiro Tourette-Syndrome Severity Scale does not assess separately motor and phonic tics, which could influence the analysis of tic severity. In the same study, individuals with TS had more often complex motor tics (55.9% vs 27.5%; p\u0026lt;0.01), copropraxia (16.2% vs 0%; p\u0026lt;0.01) and echopraxia (23.8% vs 10.0%; p\u0026lt;0.05) [15]. In the Claudio-Campos et al’s meta-analysis [3], individuals with PMTD/PVTD also had lower tic severity compared to individuals with TS (e.g. mean difference in YGTSS motor tic severity in two cohorts = −5.30, p\u0026lt;0.001; difference in YGTSS vocal tic severity in one cohort: −8.10, p\u0026lt;0.001). These studies did not look at tic-related impairment. In our sample, there was no difference in tic-related impairment, the latter being the main concern when considering treatment. We therefore question whether maintaining a distinction in classification between PMTD/PVTD and TS is relevant to patients. This is all the more true since phonic tics are simply considered by many as ‘motor tics that involve oral, nasal, pharyngeal, laryngeal and respiratory musculature’ leading to sounds [16].\u003c/p\u003e\n\u003cp\u003eThe most striking difference and the one that has been consistently reported in the literature is the difference in the comorbidity profile: individuals with PMTD/PVTD from our sample had less psychiatric comorbidity than individuals with TS (49% vs 20%, p=0.012), specifically less ADHD and OCD. It should be noted that there were no significantly more adolescent-onset cases among participants with PMTD or PVTD compared to among participants with TS. In 1995, Spencer et al [17] compared 32 children with TS and 39 children with chronic tics, who only differed in rates of OCD, oppositional defiant disorder, and simple phobia (higher rates in TS). In the Claudio Campos’ meta-analysis of 11 datasets [3], the odds of comorbid OCD and ADHD were both more than 50% lower in PMTD/PVTD compared with TS, without significant differences in mood and anxiety disorders. In the Müller-Vahl et al’s study, individuals with PMTD/PVTD had a markedly lower comorbidity score (1.9 vs. 2.7; p \u0026lt; 0.001) as compared to TS patients [15]. Previous authors suggested that TS and PMTD/PVTD are part of the same clinical spectrum with different levels of severity, PMTD/PVTD being milder forms. Our findings suggest that this is mainly driven by the severity of the comorbidities and not by tic severity. However, psychiatric comorbidity has been associated with increased tic severity [18-21]. Current and prior work show that both groups of individuals with PMTD/PVTD or TS are not treated differently. Moreover, these disorders seem to rely on the same genetic causes [22] and pathophysiological mechanisms [23].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAn interesting result was the 1.2% prevalence of ‘other specified tic disorder’ in our cohort, which was similar to the one of PVTD (1.8%). In our opinion, this term encompasses a poorly described group of individuals in the literature and adds to a complex labeling.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLimitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLimitations of our work include our monocentric design, and the relatively small number of individuals with PMTD/PVTD and of adolescent-onset. It is likely that some individuals do not remember precisely the age of onset of tics, or that they were simply not aware of them at a young age, leading us to suspect that an even smaller proportion than that observed in our sample actually had an age of onset of tics of 12 years or more. Additionally, one may criticize our choice of 12 years old to compare age at tic onset in youth. This was motivated by a desire to separate the pre/per-pubertal and post-pubertal period, and to use a threshold similar to that used in functional tic-like behaviours, so as to contrast their differences. Furthermore, we do not have the proportions of individuals who declined to participate in the Registry; it is possible that parents of children with higher number or severity of comorbidities may be more motivated to participate in research, which can influence our data. Finally, children and adolescents were included from a tertiary referral centre, therefore children with mild tics are less likely to belong to the Registry. The same is true for PMTD, PVTD and TS, therefore we do not expect this particular bias to influence our results.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eGiven that the major difference between TS and PMTD/PVTD relies on psychiatric comorbidities, which are not required for the diagnosis of the condition, we suggest making a single category for primary persistent tic disorders. This does not lessen the importance of associated symptoms for patients, which should be assessed and treated in the context of this complex neurodevelopmental disorder. Simplifying labeling may help affected individuals, their families and health-care providers by improving their understanding and acceptance of this condition. The uncommon onset of tics after the age of 12, and similarly in adulthood, and the absence of major clinical differences questions if the age limit in the diagnostic criteria would be more relevant as a supportive criterion. In a previously mentioned work, M\u0026uuml;ller-Vahl et al proposed a new term for primary tic disorders, \u0026ldquo;tic spectrum disorders\u0026rdquo; [15]. We support efforts underway to find a global term which the scientific and patient communities agree on and accurately reflects the condition [24].\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of interest:\u003c/strong\u003e none.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding or competing interests:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was received for conducting this study.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFinancial interests\u003c/em\u003e: Christelle Nilles has received research grants from the French Gilles de la Tourette Association in 2021 and in 2024. Davide Martino has received consulting honoraria from Ipsen Canada and AbbVie, lecturing honoraria from the Movement Disorders Society and the Canadian Movement Disorders Society, royalties from Oxford University Press, and research grant support from the Weston Family Foundation and the Canadian Institutes of Health Research. Julian Fletcher has no financial interests. Justyna Sarna has received consulting honoraria from AbbVie. Tamara Pringsheim has received research grant support from the Canadian Institutes of Health Research, and the Azrieli Accelerator of the University of Calgary\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eNon-financial interests:\u003c/em\u003e Christelle Nilles is an unpaid member of the Board of the European Society for the Study of Tourette syndrome (ESSTS).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis project received ethical approval from the University of Calgary Conjoint Health Research Ethics Board. Parents provided signed informed consent and children provided assent to study participation and publication of the study results.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contribution statements.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Christelle Nilles and Tamara Pringsheim. The first draft of the manuscript was written by Christelle Nilles and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAmerican Psychiatric Association (2013) Diagnostic and Statistical Manual of Mental Disorders, 5th edn. In: American Psychiatric Publishing, Washington, DC\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKnight T, Steeves T, Day L, Lowerison M, Jette N, Pringsheim T (2012) Prevalence of Tic Disorders: A Systematic Review and Meta-Analysis. 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Elsevier, pp 65\u0026ndash;108\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTammy H (2024) Tic-Talk: Voices on Tourette Labelling. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.essts.org/news/tic-talk-voices-on-tourette-labelling\u003c/span\u003e\u003cspan address=\"https://www.essts.org/news/tic-talk-voices-on-tourette-labelling\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"european-child-and-adolescent-psychiatry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ecap","sideBox":"Learn more about [European Child \u0026 Adolescent Psychiatry](http://link.springer.com/journal/787)","snPcode":"787","submissionUrl":"https://submission.nature.com/new-submission/787/3","title":"European Child \u0026 Adolescent Psychiatry","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Gilles de la Tourette syndrome, chronic motor or vocal tic disorder, tics, criteria, adolescence, attention deficit disorder with hyperactivity","lastPublishedDoi":"10.21203/rs.3.rs-6135894/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6135894/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003ePersistent motor and vocal tic disorders (PMTD/PVTD) are distinct diagnoses from Tourette syndrome (TS). In both, the threshold for the diagnosis is up to age 18, whereas tics infrequently manifest after age 12.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e In our cohort of youth with tic disorders from Calgary, Canada, we aimed to determine whether the clinical features and comorbidity profile of PMTD/PVTD differ from those of TS, and assess whether chronic tic disorders with adolescent-onset (age≥12) are different from disorders with childhood-onset (\u0026lt;12yr).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e A total of 341 children and adolescents with primary chronic tic disorders were included (90.0% with TS, 7.0% with PMTD, 1.8% with PVTD). Regarding age at tic onset, participants with adolescent-onset tics (6.7%) were diagnosed with attention-deficit/hyperactivity disorder (ADHD) more often than those with childhood-onset (p=0.02); there were no differences in sex ratio, tic severity and impairment. Regarding tic disorder diagnosis, participants with PMTD/PVTD had a later age at tic onset than those with TS (p=0.01) and had less psychiatric comorbidity (p=0.01), specifically ADHD and obsessive-compulsive disorder; there were no differences in tic severity or impairment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eGiven that the major difference between TS and PMTD/PVTD lies in psychiatric comorbidities, which are not part of the diagnostic criteria, we suggest creating a single category for primary persistent tic disorders. Tic onset in adolescence is uncommon, and coupled with the lack of any major difference in clinical features, should lead us to question whether the age limit in the diagnostic criteria might not be more relevant as a supportive criterion.\u003c/p\u003e","manuscriptTitle":"Challenging current diagnostic and classification criteria for primary tic disorders","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-11 08:44:57","doi":"10.21203/rs.3.rs-6135894/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-04-13T05:53:37+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-08T10:53:29+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-07T13:41:06+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"204029176594634143804700854662989553266","date":"2025-04-05T09:19:40+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"151235861962484877638449964622269828432","date":"2025-04-05T08:17:44+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-15T06:42:08+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-05T15:05:56+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-05T15:03:02+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Child \u0026 Adolescent Psychiatry","date":"2025-03-01T17:01:44+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-child-and-adolescent-psychiatry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ecap","sideBox":"Learn more about [European Child \u0026 Adolescent Psychiatry](http://link.springer.com/journal/787)","snPcode":"787","submissionUrl":"https://submission.nature.com/new-submission/787/3","title":"European Child \u0026 Adolescent Psychiatry","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"b3ffb03f-ee55-4250-8f77-38c041c30178","owner":[],"postedDate":"March 11th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-06-23T15:59:23+00:00","versionOfRecord":{"articleIdentity":"rs-6135894","link":"https://doi.org/10.1007/s00787-025-02732-7","journal":{"identity":"european-child-and-adolescent-psychiatry","isVorOnly":false,"title":"European Child \u0026 Adolescent Psychiatry"},"publishedOn":"2025-06-18 15:57:10","publishedOnDateReadable":"June 18th, 2025"},"versionCreatedAt":"2025-03-11 08:44:57","video":"","vorDoi":"10.1007/s00787-025-02732-7","vorDoiUrl":"https://doi.org/10.1007/s00787-025-02732-7","workflowStages":[]},"version":"v1","identity":"rs-6135894","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6135894","identity":"rs-6135894","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}