Early developmental milestones associated with tics and psychopathological comorbidity : An EMTICS study

Early developmental milestones associated with tics and psychopathological comorbidity : An EMTICS study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Early developmental milestones associated with tics and psychopathological comorbidity : An EMTICS study Tamar Steinberg, Dana Feldman-Sadeh, Alan Apter, Yael Bronstein, and 13 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5368250/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 17 Jul, 2025 Read the published version in European Child & Adolescent Psychiatry → Version 1 posted 11 You are reading this latest preprint version Abstract Background Chronic Tic disorders (CTD) including Tourette Syndrome (TS), are associated with psychopathological comorbidities. Attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and other comorbidities have been linked to delays in early developmental milestones. Few studies have investigated the relationship between early developmental milestones, tic severity, and related comorbidities. Methods 383 participants aged 3–16 years (76.8%, n = 294 boys) with CTD from the baseline assessment of the European Multicenter Tics in Children Study (EMTICS), were evaluated for early developmental milestones (sitting, walking, first words, complete a sentence, bladder and bowel control), tic severity, tic-related functional impairment, obsessive-compulsive disorder (OCD), ADHD, oppositional defiant disorder (ODD) and suspected ASD. Data was collected using gold-standard self and clinician reporting instruments. Analyses included Pearson correlations and logistic regressions. Results Correlations between the acquisition of developmental milestones and tic severity or impairment were significant with small effect sizes (severity of motor tics and tic impairment were correlated with walking (r = .11), while vocal tics were correlated with first words (r = .12)). Logistic regression revealed that delayed acquisition of first words was significantly associated with ADHD, ODD and suspected ASD (Odds Ratio (ROR): 1-1.13, 1.05–1.21, 1.01–1.16, 1.04–1.22, respectively), while delayed walking acquisition was associated with OCD (ROR: 1.01–1.27). Discussion This study highlights the association between early developmental milestones and later psychopathological comorbidities in CTD patients. These findings emphasize the need for further research to distinguish between children with only tics and those with tics and psychopathological comorbidities, to improve early detection of individuals at risk. Developmental milestones Tourette syndrome Tic disorders attention deficit disorder (ADHD) Obsessive compulsive disorder (OCD) Introduction Chronic Tic Disorders (CTD), including Tourette Syndrome (TS), are neurodevelopmental conditions characterized by the persistent presence of sudden, rapid, recurrent, non-rhythmic motor movements and/or vocalizations lasting at least one year with onset before the age of 18 [ 1 , 2 ]. TS typically manifests early in life and is frequently accompanied by high rates of psychopathological comorbid conditions throughout an individual's lifespan [ 3 , 4 ]. The most common comorbidity is attention deficit/hyperactivity disorder (ADHD), followed by obsessive-compulsive disorder (OCD) and autism spectrum disorder (ASD) [ 5 ]. Other associated comorbidities include mood disorders, anxiety disorders, oppositional defiant disorders (ODD) and various disruptive, impulse-control, and conduct disorders [ 6 – 10 , 5 ]. Psychopathological comorbidities, such as ADHD and ASD have been linked to delays in early developmental milestones [ 11 – 14 ]. Furthermore, TS patients with psychopathological comorbidities, such as communication disorders and ADHD, may exhibit significant delays in motor and language acquisition [ 15 ]. Studies have suggested that these delays may stem from less efficient brain connectivity among brain regions [ 16 ]. Additionally, shared factors such as prenatal, birth and postnatal complications may contribute to both CTD and developmental delays [ 17 – 19 ]. Developmental delays were also associated with other psychopathological comorbidities. For instance, children with anxiety disorders have been found to exhibit higher rates of developmental delays in areas such as speech, motor, or bladder and bowel control [ 20 ]. Similarly, parents of children with ODD have reported developmental difficulties in bladder/bowel control and language, including delays in speaking their first words [ 21 ]. The United Kingdom-based AVON longitudinal birth cohort study further reveled that children with obsessions and compulsions had significantly higher rates of soiling, indicating developmental challenges associated with OCD [ 22 ]. The Copenhagen Perinatal Cohort longitudinal study demonstrated that delayed acquisition of motoric milestones, including sitting and walking, was correlated with later onset of adult schizophrenia [ 20 ]. These findings highlight the importance of monitoring developmental milestones during childhood to identify individuals at risk for future psychopathological comorbidities. Despite these findings, research on the association between developmental milestones and core features of TS remains limited. A notable study by Comings and Comings (1987) found no significant delays in walking or talking among individuals with TS compared to controls; however, there was a significant delay in toilet training in most TS patients. This study did not take into account tic severity or psychopathological comorbidities [ 23 ]. More recent studies have shown that developmental delays are more common in individuals with both TS and psychopathological comorbidities, such as ADHD, compared to those with TS alone [ 15 , 24 ] Given the limited research, the connection between developmental delays and later-life tic severity and psychopathological comorbidities remains inconclusive. To address this gap, we retrospectively examined early developmental milestones in a large sample of youth (ages 3–16) with chronic tics from the European Multicenter Tics in Children Study (EMTICS) [ 25 ]. Our study aimed to investigate the developmental milestones of individuals with chronic CTDs. Specifically, we sought to explore the relationship between the age of acquiring early developmental milestones (motor, language, and toilet training) and both tic severity and impairment, as well as psychopathological comorbidities, including OCD, ADHD, ODD, and suspected ASD. We hypothesized that delayed acquisition of these milestones would predict greater tic severity and impairment, along with more severe comorbid symptoms or higher rates of comorbid psychopathologies. Methods Participants and Procedure The sample included 383 children and adolescents aged 3 to 16 years with Tourette syndrome (TS) or chronic tic disorder (CTD) who participated in the baseline assessment of the EMTICS study, which investigates the role of genetic, autoimmune, and psychosocial factors in the onset and progression of tics [ 23 ]. Participants were recruited from sixteen child mental health or pediatric neurology outpatient clinics across Europe and Israel, as well as through advertisements directed at patient organizations and health professionals. All participants who met the diagnostic criteria for TS or CTD according to the DSM-IV-TR (American Psychiatric Association) were invited, along with their parents or guardians, to participate in the study [ 1 ]. Inclusion criteria required participants to be between 3 and 16 years old, with a confirmed diagnosis of TS or CTD based on DSM-IV-TR criteria [ 1 ]. Additionally, for the current study, only participants whose parents had completed all questions related to early developmental milestones were included. Exclusion criteria included severe medical or neurological illness, recent antibiotic treatment within the past month, or inability to comply with study procedures. Written informed consent was obtained from parents or legal guardians, and participating adolescents provided either written assent or consent, depending on local medical-ethical regulations. Ethical approval was granted by the relevant Research Ethics Committees at each participating center. Baseline measures, including parent-reported questionnaires and a clinical interview, were collected during the initial EMTICS visit. Additionally, a clinician confirmed the diagnosis of TS or CTD and assessed for ADHD and OCD according to DSM-IV-TR criteria [ 1 ]. Measures Demographic information , including the child's sex, age at evaluation, study site, and ethnicity, was collected through a demographic questionnaire . Early Developmental Milestones were gathered using the Modified Schedule for Risk and Protective Factors in Early Development (MSRPFED) [ 24 ]. Parents reported the age (in months) at which their child acquired eight developmental milestones from early life: sitting, walking, first words, sentence completion, daytime and nighttime bladder control, and bowel control. This information created eight continuous developmental measures for analysis. Developmental delays were assessed using the Denver II assessment for motor and language development [ 24 ], with suspected delays determined using the 90th percentile age norms. Toilet training and delays differentiated by sex were assessed based on the 75th percentile, following the methodology of Schum et al. [ 25 ]. Consequently, an additional dichotomous variable was created for each developmental milestone to identify children with developmental delays. Tic severity and impairment symptoms were measured using the clinician-rated Yale Global Tic Severity Scale (YGTSS) [ 26 , 27 ]. Each of the following dimensions was rated on a five-point scale: number, frequency, intensity, interference, and complexity over the past week. Scores were calculated for motor tic severity (range: 0–25), vocal tic severity (range: 0–25), total tic severity (range: 0–50), and the tic impairment score (subjective evaluation of impairment caused by tics, range: 0–50). In the current study, Cronbach’s alpha values were calculated as follows: α = .88 for the total tic severity scale, α = .82 for the motor subscale, and α = .89 for the vocal subscale. Total tic severity cut-offs were defined as follows: minimal tics < 10, mild tics: 10–20, moderate tics: 20–40, and severe tics: 40–50, based on the work of Leckman and colleagues [ 26 ]. Obsessive-Compulsive Disorder (OCD) symptoms were assessed using the clinician-rated Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) [ 32 ], which evaluates five dimensions: time, interference, distress, resistance, and control associated with obsessions and compulsions over the past week. Each dimension is rated on a five-point scale. The scale provides three summary scores: obsession severity (ranging from 0 to 20; α = .92), compulsion severity (ranging from 0 to 20; α = .93), and total OCD severity (ranging from 0 to 40; α = .94). A dichotomous diagnosis of OCD was based on DSM-IV-TR criteria, as determined by a trained clinician, or a CY-BOCS total severity score of 16 or higher, following the cut-off established by Scahill et al. [ 28 ]. Attention Deficit/Hyperactivity Disorder (ADHD) symptoms were assessed using the abbreviated version of the Swanson, Nolan, and Pelham, version IV (SNAP-IV) rating scale, which evaluates symptoms over the past week on a four-point scale. This scale yields three scores: inattention score (9 items, range 0–27; current study α = .91), hyperactivity-impulsivity score (9 items, range 0–27; α = .90), and combined score (18 items, range 0–54; current study α = .94), with higher scores indicating greater symptom severity [ 29 ]. A dichotomous diagnosis of ADHD was determined based on DSM-IV-TR criteria, as diagnosed by a trained clinician, and included any of the ADHD subtypes (inattentive, hyperactive, or combined) [ 30 ]. Oppositional Defiant Disorder (ODD) symptoms were assessed using the parent-rated Swanson, Nolan, and Pelham, version IV (SNAP-IV) abbreviated version rating scale. ODD symptoms were evaluated over the past week on a four-point scale, with higher scores indicating greater symptom severity (8 items, range 0–24; current study α = .91). A dichotomous ODD variable was defined as scoring above the 95th percentile cut-off on the SNAP-IV questionnaire (ODD mean score ≥ 1.88) [ 30 ]. Suspected Autism Spectrum Disorder (ASD) symptoms were assessed using the parent-rated Autism Spectrum Screening Questionnaire (ASSQ) [ 31 ]. A three-point scale was employed to evaluate symptoms across four domains: social interaction, communication, restricted and repetitive behaviors, and motor clumsiness, along with other associated symptoms. Higher scores indicated greater suspected ASD symptom severity (27 items, range 0–54; α = .90). A dichotomous variable for suspected ASD was defined as scoring above the established cut-off (ASSQ score ≥ 19) [ 31 ]. Statistical analysis Missing data patterns were examined using Little's MCAR (Missing Completely at Random) test, incorporating variables such as developmental milestones, tics, OCD, ADHD, ODD, suspected ASD, sex, age at visit, ethnicity, and site. A correlation matrix was created to assess the relationships between early developmental milestones, tic severity and impairment, and the severity of psychopathological comorbidity symptoms (all continuous variables). Due to the weak correlations with continuous variables, we proceeded with our analysis using dichotomous dependent variables for ADHD, OCD, and ODD (based on DSM-IV-TR criteria or established cut-offs from gold standard report measures). To evaluate whether developmental milestones are related to the presence of psychopathological comorbid diagnoses, logistic regression analyses were performed separately for each diagnosis, with the presence of ADHD, ODD, OCD, and suspected ASD as dependent variables (0 = without the respective comorbidity; 1 = with the respective comorbidity). Independent variables included the age in months for each developmental milestone (sitting, walking, first words, sentence completion, daytime/nighttime bladder control, and bowel control). Covariates such as sex, age, and site were also included. Results were reported using odds ratios (OR), where OR values below, equal to, or above 1 reflect lower, neutral, or higher odds of the outcome, respectively. Model accuracy was evaluated using a classification table to compare observed and predicted outcomes. All analyses were conducted using IBM SPSS, Version 20.0 [ 34 ], with a significance level of α = .05. Results Sample characteristics The initial sample consisted of 709 participants. Only participants whose parents had completed all questions related to early developmental milestones were included. Missing data were assessed using Little's MCAR test (considering variables such as sex, age at visit, ethnicity, study site, tics, OCD, ADHD, ODD, and suspected ASD), which indicated that the missing data were completely random (χ²(523) = 564.26, p = .10). To validate this result, differences in outcome variables between participants with complete data and those who were excluded were examined using t-tests. Although significant differences were found for nighttime bowel control and ADHD (with higher scores for excluded participants), the effect sizes were relatively small (Cohen's d ≤ .2). The final sample included 383 participants. The majority of participants (87.5%, n = 335) were diagnosed with Tourette syndrome (TS), 11.5% (n = 44) with chronic motor tic disorder, and less than 1% (n = 1; 0.3%) with chronic vocal tic disorder. In terms of tic severity, 47% (n = 180) of participants exhibited moderate tic severity, 36% (n = 138) had mild tics, 16.2% (n = 62) had minimal tics, and 0.8% (n = 3) had severe tics. Descriptive statistics for demographics, tic severity, impairment, and comorbid psychopathology symptoms are presented in Table 1 . Table 1 Demographics and clinical characteristics (n = 383) M ± SD N (%) Range Age 10.67 ± 2.69 3.35–16.79 Sex (male) 294 (76.8) - Ethnicity (Caucasian) 362 (94.5) - Chronic tic disorder Motor tic severity score a 12.42 ± 4.55 0–23 Vocal tic severity score a 7.40 ± 5.55 0–22 Total tic severity score a 19.81 ± 8.70 0–44 Tic impairment score a 14.73 ± 11.68 0–50 OCD b 121 (31) Obsessions severity score b 3.20 ± 4.69 0–17 Compulsions severity score b 3.85 ± 4.99 0–20 Total OCD severity score b 7.04 ± 8.85 0–34 ADHD 96 (25.1) Inattention severity score c 10.59 ± 6.91 0–27 Hyperactivity severity score c 8.87 ± 6.76 0–27 Combined severity score c 19.46 ± 12.58 0–54 ODD c ODD severity score 8.23 ± 5.96 49 (12.8) 0–24 Suspected ASD d 11.06 ± 8.93 72 (18.8) 0–46 Suspected ASD severity score 64 (16.7) Abbreviations: OCD, Obsessive Compulsive Disorder; ADHD, Attention Deficit Hyperactive Disorder; ODD, Oppositional Defiant Disorder; suspected ASD, suspected Autism Spectrum Disorder; a by YGTSS – Yale Global Tic Severity Scale; b by CYBOCS – Children’s Yale-Brown Obsessive Compulsive Scale; c by SNAP – Swanson, Nolan and Pelham; d by ASSQ – Autism Spectrum Screening Questionnaire. Early developmental milestones Table 2 presents the average age at which participants achieved early developmental milestones, as well as the percentage of participants with suspected delays. Daytime and nighttime bowel control were highly correlated (r = .83, p < .01) and were therefore combined into a single variable for further analysis based on clinical considerations. Table 3 shows inter-correlations between developmental milestones, with significant positive correlations within each domain (motor, language, and toilet training; r = .39–.67, p < .01). Cross-domain correlations ranged from minor to moderate positive (r = .02–.46, p = n.s.–< .01). Table 2 Age of acquiring early developmental milestones (n = 383) Developmental milestones Md (months) M ± SD (months) Range (months) Suspected developmental delay % (n) Motor development Sitting 6.00 6.84 ± 1.54 3–12 2.9 (11) a Walking 12.50 13.01 ± 2.48 8.5–36 8.1 (31) a Language development First words 12.00 13.28 ± 5.98 4–52 19.8 (76) a Complete a sentence 22.00 21.95 ± 7.58 8–60 18.3 (70) a Toilet training Day bladder control 30.00 30.80 ± 13.87 10–168 8.9 (34) b Night bladder control 30.00 37.34 ± 21.70 12–192 19.1 (73) b Bowel control 30.00 31.85 ± 10.72 12–134 15.4 (59) b a According to The Denver II Developmental Screening Test (1992) [ 28 ]. b According to Schum, et al (2002) [ 29 ]. Table 3 Correlation matrix of intra-correlations between early developmental milestones (n = 383) Domain Developmental milestones Walking First words Complete a sentence Day bladder control Night bladder control Bowel control Motor Sitting .40** .22** .06 .08 .08 .16** Walking -- .46** .28** .09 .06 .14** Language First words -- .68** .12* .09 .25** Complete a sentence -- .09 .02 .22** Toilet training Day bladder control -- .67** .59** Night bladder control -- .46** Bowel control -- * p < .05, ** p < .01 Correlations between early acquisition of developmental milestones, tics, and comorbid symptoms A Pearson correlation analysis (Table 4) revealed weak correlations overall, with small effect sizes (r < .21). Notably, the acquisition of sitting was not associated with any comorbid psychopathological symptoms. Motor tics and tic impairment were correlated with walking (r = .11–.12), while vocal tics were correlated with first words (r = .12). OCD showed correlations with walking, first words, and sentence completion (r = .12–.18). ADHD was correlated with walking, first words, sentence completion, and bowel control (r = .12–.21). ODD was correlated with first words (r = .15), and suspected ASD was correlated with bladder and bowel control (r = .10–.17). תחתית הטופס Table 4 Correlation matrix between early developmental milestones and severity of tics and comorbid psychopathology symptoms (n = 383) Age of acquiring early developmental milestones (months) Sitting Walking First words Complete a sentence Day bladder control Night bladder control Bowel control Tics a Motor tic severity − .04 .11* .02 .05 .04 − .003 .01 Vocal tic severity − .09 .06 .12* .08 .05 − .007 .08 Total tic severity − .08 .09 .08 .07 .06 − .004 .06 Impairment − .04 .12* .08 .07 .07 .03 .09 OCD severity b Obsessions .01 .16** .15** .12** .04 − .05 .05 Compulsions .005 .17** .07 .08 .03 − .02 .05 Total OCD severity .0 1 .18** .12* .11* .03 − .04 .05 ADHD severity c Inattention .09 .18** .18** .13* .07 .06 .1* Hyperactivity .06 .16** .21** .12* .04 .06 .11* Combined .08 .19** .21** .13** .06 .06 .12* ODD severity c − .05 .08 .15** .09 − .008 − .01 .02 ASD severity d .08 .05 .1 .03 .17** .17** .10* * p < .05, ** p < .01 Abbreviations: OCD, Obsessive Compulsive Disorder; ADHD, Attention Deficit Hyperactive Disorder; suspected ASD, suspected Autism Spectrum Disorder; ODD, Oppositional Defiant Disorder. a by YGTSS – Yale Global Tic Severity Scale; b by CYBOCS – Children’s Yale-Brown Obsessive Compulsive Scale; c by SNAP – Swanson, Nolan and Pelham; d by ASSQ – Autism Spectrum Screening Questionnaire. Prediction of psychopathological comorbidity diagnoses by early developmental milestones Logistic regression analyses were conducted to explore the relationship between early developmental milestones and comorbid psychopathological diagnoses (Table 5), with the results detailed below. Unless otherwise noted, the covariates (sex, age, and site) were not significant OCD : The model was significant (χ²(10) = 34.2, p < .01), accounting for 12.2% of the variance in OCD and correctly classifying 68.7% of cases. Later acquisition of walking (OR = 1.13; 1.01–1.27, p < .05) and the child's older age (covariate) (OR = 1.16; 1.06–1.26, p < .01) increased the likelihood of an OCD diagnosis. ADHD : The model predicting ADHD was also significant (χ²(10) = 22.97, p < .01), accounting for 8.6% of the variance and correctly classifying 75% of cases. Later acquisition of first words increased the likelihood of an ADHD diagnosis (OR = 1.06; 1.00–1.30, p < .05), while later acquisition of sentence completion reduced the likelihood (OR = 0.95; 0.91–0.99, p < .05). ODD : Significant results were found (χ²(10) = 25.11, p < .05), contributing 11.9% to the variance in ODD and correctly classifying 87.2% of cases. Later acquisition of first words increased the likelihood of ODD (OR = 1.13; 1.04–1.22, p < .01), while later acquisition of sitting reduced the likelihood (OR = 0.70; 0.54–0.90, p < .01). Being male (covariate) also increased the likelihood of an ODD diagnosis (OR = 0.36; 0.14–0.90, p < .03). Suspected ASD : The model was significant (χ²(10) = 34.32, p < .01), accounting for 13.8% of the variance in suspected ASD and correctly classifying 81.2% of cases. Later acquisition of first words increased the likelihood of suspected ASD (OR = 1.13; 1.05–1.21, p < .01), while sentence completion reduced the likelihood (OR = 0.95; 0.89–1.00, p < .05). Table 5 Logistic Regressions for predicting comorbid psychopathology diagnoses by early developmental milestones Prediction of OCD by: B SE Wald p Exp(B) (95% C.I) NagelkerkeR 2 Overall Sitting − .08 .08 .94 .33 .92 (.78–1.09) .122 Walking .12 .06 4.24 .04 1.13 (1.01–1.27) First words .04 .03 1.94 .16 1.04 (.98–1.10) Complete sentence .00 .02 .00 1.00 1.00 (.96–1.04) Day bladder control .02 .01 2.37 .12 1.02 (.99–1.05) Night bladder control − .01 .01 2.80 .09 .99 (.97–1.00) Bowel control .01 .01 .28 .60 1.01 (.98–1.03) Prediction of ADHD by : B SE Wald p Exp(B) (95% C.I) NagelkerkeR 2 Overall Sitting − .03 .09 .16 .69 .97 (.82–1.14) .086 Walking .12 .06 3.66 .06 1.12 (1.00–1.27) First words .06 .03 3.83 .05 1.06 (1.00–1.13) Complete sentence − .05 .02 4.01 .05 .95 (.91–1.00) Day bladder control − .03 .03 .97 .32 .98 (.93–1.03) Night bladder control .00 .01 .19 .67 1.00 (.98–1.01) Bowel control .05 .02 3.52 .06 1.05 (.98–1.10) Prediction of suspected ASD by : B SE Wald p Exp(B) (95% C.I) NagelkerkeR 2 Overall Sitting .086 .09 .22 .64 1.05 (.87–1.26) .138 Walking − .09 .07 1.99 .16 .91 (.80–1.04) First words .12 .04 11.34 .00 1.13 (1.05–1.21) Complete sentence − .06 .03 3.75 .05 .95 (.89–1.00) Day bladder control .01 .01 .33 .57 1.01 (.98–1.04) Night bladder control .01 .01 2.09 .15 1.01 (1.00–1.03) Bowel control − .01 .02 .70 .40 .99 (.96–1.02) Prediction of ODD by : B SE Wald p Exp(B) (95% C.I) NagelkerkeR 2 Overall Sitting − .36 .13 7.53 .01 .70 (.54 – .90) .119 Walking .07 .07 1.03 .31 1.07 (.94–1.23) First words .12 .04 8.74 .00 1.12 (1.04–1.22) Complete sentence − .06 .03 3.30 .07 .94 (.88–1.00) Day bladder control − .04 .05 .68 .41 .96 (.88–1.05) Night bladder control .00 .01 .19 .66 1.00 (.98–1.02) Bowel control .02 .04 .16 .68 .1.02 (.94–1.09) Note: the models covaried sex site and age (significant results are presented in the main text). Abbreviations: ADHD, Attention Deficit Hyperactive Disorder; OCD, Obsessive Compulsive Disorder; suspected ASD, suspected Autism Spectrum Disorder; ODD, Oppositional Defiant Disorder. Discussion The current study included a large sample of children and adolescents aged 3–16 years with chronic tic disorders (CTD), aimed to explore the relationship between delayed acquisition of key developmental milestones (motor, language, and toilet training) and tic severity, tic-related impairment as well as psychopathological comorbidities. The primary finding was that delayed language acquisition, particularly speaking first words in infancy, predicted later psychopathological comorbidities associated with CTD, including OCD, ADHD, ODD and suspected ASD. In line with our hypothesis, tic severity and impairment were correlated with developmental milestones albeit with small effect size. Interestingly, motor tics and tic impairment were associated with the age of first walking, while vocal tics were linked to delayed acquisition of first words. Similarly, Cravedi et al., (2018), identified developmental delays in children with tics and neurodevelopmental comorbidities, however, their study categorized TS individuals into clusters rather than using continuous measures [15]. In contrast, Coming and Comings (1987), in a different study design, found no significant delays in talking or walking among TS patients compared to controls, but reported significant delays in bladder and bowel control [32]. These methodological differences may explain the variance in findings between studies. Thus, further research is needed to draw definitive conclusions. Regarding related psychopathological comorbidities, our findings revealed a correlation between OCD, both severity and diagnosis, and delays in motor (walking) and language development. This aligns with previous research indicating that children with anxiety, a common comorbidity of OCD, often experience developmental delays in motor, language, and toilet training milestones [20, 33, 34] Importantly, this study focused on tic-related OCD, and future research should further explore developmental delays in cases of non-tic-related OCD [35, 36]. Our findings corroborate previous research that links neurodevelopmental disorders to developmental delays [14, 37, 38]. Specifically, we found that delayed language acquisition and bowel control were both associated with the severity of ADHD and suspected ASD symptoms. This aligns with LeBeau et al. (2022), who reported that bowel control difficulties were linked to the severity of ADHD and ASD symptoms, while delayed speech acquisition predicted later ASD diagnoses [11]. Similarly, Gurevitz et al. (2012) identified language delay as a significant early predictor of ADHD [39, 40]. Regarding ODD, our study found a significant correlation between delayed acquisition of first words and later ODD diagnosis and severity of symptoms . This aligns with previous research showing that children with ODD often experience slower language development and less speech clarity [22]. Nevertheless more studies on ODD with or without TS are needed. Interestingly, negative correlations were found between ADHD and suspected ASD diagnoses with sentence completion, as well as between ODD diagnoses and sitting. One possible explanation is that children with psychopathological comorbidities often exhibit highly variable developmental trajectories, resulting in uneven progress across different developmental domains. For example, LeBeau et al. (2022) identified a similar pattern, particularly noting negative correlations between ADHD and delayed language acquisition [11]. Another explanation may lie in the tendency of parents to more easily recall prominent milestones, such as first words or walking, compared to less noticeable ones like sentence completion or sitting. This highlights the potential influence of memory bias in parental reporting of developmental milestones. This study highlights the association between early developmental delays, including language, motor acquisition, and bowel/bladder control, and the later development of psychopathological comorbidities (OCD, ADHD, ODD, and suspected ASD) in CTD patients. Identifying these relationships could improve early detection of at-risk individuals and facilitate timely, tailored interventions, potentially improving long-term outcomes and quality of life for CTD patients with comorbid psychopathologies. Furthermore, our findings underscore the importance of distinguishing between patients with tics alone and those with both tics and comorbid psychopathologies, as demonstrated in previous studies Top of Form[3, 6, 40]. Strengths and Limitations While this study benefited from a substantial sample size, several limitations should be considered. First, most participants were recruited from clinics, which may have introduced selection bias, resulting in a higher proportion of individuals with psychopathological comorbidities compared to the general population. Second, the assessment of developmental delays was retrospective and relied on parental reports, potentially introducing memory bias [41]. Third, given the challenge of establishing universally applicable developmental norms, we relied on commonly accepted norms from validated assessment tools used in child developmental centers. Additionally, the absence of a healthy control group and a group with similar psychopathological comorbidities but without tics limits our ability to make broader comparisons. Finally, the potential impact of multiple comparisons on the results should be acknowledged. However, the consistency of patterns across our statistical analyses, particularly concerning language delays and their relationship with symptom severity, supports the robustness of our findings. Future studies should adopt a prospective design with a healthy control group and long-term follow-up from infancy to minimize recall bias and provide a more comprehensive understanding of the relationship between developmental milestones and psychopathological comorbidities. Declarations Acknowledgement & Funding: The authors are deeply grateful to all the children and their parents who willingly participated to make this research possible. The longitudinal European Multicenter Tics in Children Study (EMTICS) has received funding from the European Union’s Seventh Framework Program for research, technological development, and demonstration under Grant agreement no. 278367. Declarations of Interest: None References Diagnostic and statistical manual of mental disorders: DSM-5 TM , 5th ed. American Psychiatric Publishing, Inc., Arlington, VA, US Bloch MH, Leckman JF (2009) Clinical course of Tourette syndrome. Journal of Psychosomatic Research 67:497–501. https://doi.org/10.1016/j.jpsychores.2009.09.002 Hirschtritt ME, Lee PC, Pauls DL, et al (2015) Lifetime Prevalence, Age of Risk, and Genetic Relationships of Comorbid Psychiatric Disorders in Tourette Syndrome. JAMA Psychiatry 72:325–333. https://doi.org/10.1001/jamapsychiatry.2014.2650 Groth C, Mol Debes N, Rask CU, et al (2017) Course of Tourette Syndrome and Comorbidities in a Large Prospective Clinical Study. 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Eur Child Adolesc Psychiatry 21:451–457. https://doi.org/10.1007/s00787-012-0278-5 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. Journal of Child and Adolescent Psychopharmacology 27:243–249. https://doi.org/10.1089/cap.2016.0120 Freeman RD, Fast DK, Burd L, et al (2000) An international perspective on Tourette syndrome: selected findings from 3500 individuals in 22 countries. Developmental Medicine & Child Neurology 42:436–447. https://doi.org/10.1111/j.1469-8749.2000.tb00346.x LeBeau B, Schabilion K, Assouline SG, et al (2022) Developmental milestones as early indicators of twice-exceptionality. Neurobiology of Learning and Memory 194:107671. https://doi.org/10.1016/j.nlm.2022.107671 Lee J, Mayall LA, Bates KE, et al (2021) The relationship between motor milestone achievement and childhood motor deficits in children with Attention Deficit Hyperactivity Disorder (ADHD) and children with Developmental Coordination Disorder. Research in Developmental Disabilities 113:103920. https://doi.org/10.1016/j.ridd.2021.103920 Uljarević M, Hedley D, Alvares GA, et al (2017) Relationship between early motor milestones and severity of restricted and repetitive behaviors in children and adolescents with autism spectrum disorder. Autism Research 10:1163–1168. https://doi.org/10.1002/aur.1763 Kuo SS, van der Merwe C, Fu JM, et al (2022) Developmental Variability in Autism Across 17 000 Autistic Individuals and 4000 Siblings Without an Autism Diagnosis: Comparisons by Cohort, Intellectual Disability, Genetic Etiology, and Age at Diagnosis. JAMA Pediatrics 176:915–923. https://doi.org/10.1001/jamapediatrics.2022.2423 Cravedi E, Deniau E, Giannitelli M, et al (2018) Disentangling Tourette syndrome heterogeneity through hierarchical ascendant clustering. Developmental Medicine & Child Neurology 60:942–950. https://doi.org/10.1111/dmcn.13913 Openneer TJC, Marsman J-BC, van der Meer D, et al (2020) A graph theory study of resting-state functional connectivity in children with Tourette syndrome. Cortex 126:63–72. https://doi.org/10.1016/j.cortex.2020.01.006 Abdulkadir M, Tischfield JA, King RA, et al (2016) Pre- and perinatal complications in relation to Tourette syndrome and co-occurring obsessive-compulsive disorder and attention-deficit/hyperactivity disorder. J Psychiatr Res 82:126–135. https://doi.org/10.1016/j.jpsychires.2016.07.017 Brander G, Rydell M, Kuja-Halkola R, et al (2018) Perinatal risk factors in Tourette’s and chronic tic disorders: a total population sibling comparison study. Mol Psychiatry 23:1189–1197. https://doi.org/10.1038/mp.2017.31 Ergaz Z, Ornoy A (2011) Perinatal and Early Postnatal Factors Underlying Developmental Delay and Disabilities. Developmental Disabilities Research Reviews 17:59–70. https://doi.org/10.1002/ddrr.1101 Johnco C, Lewin AB, Salloum A, et al (2016) Adverse Prenatal, Perinatal and Neonatal Experiences in Children with Anxiety Disorders. Child Psychiatry Hum Dev 47:317–325. https://doi.org/10.1007/s10578-015-0569-4 Joinson C, Heron J, Butler U, et al (2006) Psychological Differences Between Children With and Without Soiling Problems. Pediatrics 117:1575–1584. https://doi.org/10.1542/peds.2005-1773 Martel MM (2019) The Clinician’s Guide to Oppositional Defiant Disorder: Symptoms, Assessment, and Treatment. Academic Press Schrag A, Martino D, Apter A, et al (2019) European Multicentre Tics in Children Studies (EMTICS): protocol for two cohort studies to assess risk factors for tic onset and exacerbation in children and adolescents. Eur Child Adolesc Psychiatry 28:91–109. https://doi.org/10.1007/s00787-018-1190-4 Frankenburg WK, Dodds J, Archer P, et al (1992) The Denver II: A Major Revision and Restandardization of the Denver Developmental Screening Test. Pediatrics 89:91–97. https://doi.org/10.1542/peds.89.1.91 Schum TR, Kolb TM, McAuliffe TL, et al (2002) Sequential Acquisition of Toilet-Training Skills: A Descriptive Study of Gender and Age Differences in Normal Children. Pediatrics 109:e48. https://doi.org/10.1542/peds.109.3.e48 Leckman JF, Riddle MA, Hardin MT, et al (1989) The Yale Global Tic Severity Scale: Initial Testing of a Clinician-Rated Scale of Tic Severity. Journal of the American Academy of Child & Adolescent Psychiatry 28:566–573. https://doi.org/10.1097/00004583-198907000-00015 Storch EA, Murphy TK, Geffken GR, et al (2005) Reliability and validity of the Yale Global Tic Severity Scale. Psychological Assessment 17:486–491. https://doi.org/10.1037/1040-3590.17.4.486 Scahill L, Riddle MA, McSWIGGIN-HARDIN M, et al (1997) Children’s Yale-Brown Obsessive Compulsive Scale: Reliability and Validity. Journal of the American Academy of Child & Adolescent Psychiatry 36:844–852. https://doi.org/10.1097/00004583-199706000-00023 Gau SS-F, Shang C-Y, Liu S-K, et al (2008) Psychometric properties of the Chinese version of the Swanson, Nolan, and Pelham, version IV scale – parent form. International Journal of Methods in Psychiatric Research 17:35–44. https://doi.org/10.1002/mpr.237 Bussing R, Fernandez M, Harwood M, et al (2008) Parent and Teacher SNAP-IV Ratings of Attention Deficit Hyperactivity Disorder Symptoms: Psychometric Properties and Normative Ratings From a School District Sample. Assessment 15:317–328. https://doi.org/10.1177/1073191107313888 Ehlers S, Gillberg C, Wing L (1999) A Screening Questionnaire for Asperger Syndrome and Other High-Functioning Autism Spectrum Disorders in School Age Children. J Autism Dev Disord 29:129–141. https://doi.org/10.1023/A:1023040610384 Comings DE, Comings BG (1987) A controlled study of Tourette syndrome. VI. Early development, sleep problems, allergies, and handedness. Am J Hum Genet 41:822–838 Goodwin GM (2015) The overlap between anxiety, depression, and obsessive-compulsive disorder. Dialogues in Clinical Neuroscience 17:249–260. https://doi.org/10.31887/DCNS.2015.17.3/ggoodwin Comer JS, Kendall PC, Franklin ME, et al (2004) Obsessing/worrying about the overlap between obsessive–compulsive disorder and generalized anxiety disorder in youth. Clinical Psychology Review 24:663–683. https://doi.org/10.1016/j.cpr.2004.04.004 Brander G, Kuja-Halkola R, Rosenqvist MA, et al (2021) A population-based family clustering study of tic-related obsessive-compulsive disorder. Mol Psychiatry 26:1224–1233. https://doi.org/10.1038/s41380-019-0532-z Leckman JF, Denys D, Simpson HB, et al (2010) Obsessive–compulsive disorder: a review of the diagnostic criteria and possible subtypes and dimensional specifiers for DSM-V. Depression and Anxiety 27:507–527. https://doi.org/10.1002/da.20669 Flensborg-Madsen T, Mortensen EL (2018) Associations of Early Developmental Milestones With Adult Intelligence. Child Development 89:638–648. https://doi.org/10.1111/cdev.12760 Perna R, Loughan A (2012) Early Developmental Delays: Neuropsychological Sequelae and Subsequent Diagnoses. Applied Neuropsychology: Child 1:57–62. https://doi.org/10.1080/09084282.2011.643963 Gurevitz M, Geva R, Varon M, Leitner Y (2014) Early Markers in Infants and Toddlers for Development of ADHD. J Atten Disord 18:14–22. https://doi.org/10.1177/1087054712447858 Mathews CA, Grados MA (2011) Familiality of Tourette Syndrome, Obsessive-Compulsive Disorder, and Attention-Deficit/Hyperactivity Disorder: Heritability Analysis in a Large Sib-Pair Sample. Journal of the American Academy of Child & Adolescent Psychiatry 50:46–54. https://doi.org/10.1016/j.jaac.2010.10.004 Tanur JM (1992) Questions About Questions: Inquiries into the Cognitive Bases of Surveys. Russell Sage Foundation Additional Declarations No competing interests reported. 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TS typically manifests early in life and is frequently accompanied by high rates of psychopathological comorbid conditions throughout an individual's lifespan [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The most common comorbidity is attention deficit/hyperactivity disorder (ADHD), followed by obsessive-compulsive disorder (OCD) and autism spectrum disorder (ASD) [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Other associated comorbidities include mood disorders, anxiety disorders, oppositional defiant disorders (ODD) and various disruptive, impulse-control, and conduct disorders [\u003cspan additionalcitationids=\"CR7 CR8 CR9\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e–\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePsychopathological comorbidities, such as ADHD and ASD have been linked to delays in early developmental milestones [\u003cspan additionalcitationids=\"CR12 CR13\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e–\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Furthermore, TS patients with psychopathological comorbidities, such as communication disorders and ADHD, may exhibit significant delays in motor and language acquisition [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Studies have suggested that these delays may stem from less efficient brain connectivity among brain regions [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Additionally, shared factors such as prenatal, birth and postnatal complications may contribute to both CTD and developmental delays [\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e–\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDevelopmental delays were also associated with other psychopathological comorbidities. For instance, children with anxiety disorders have been found to exhibit higher rates of developmental delays in areas such as speech, motor, or bladder and bowel control [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Similarly, parents of children with ODD have reported developmental difficulties in bladder/bowel control and language, including delays in speaking their first words [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The United Kingdom-based AVON longitudinal birth cohort study further reveled that children with obsessions and compulsions had significantly higher rates of soiling, indicating developmental challenges associated with OCD [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The Copenhagen Perinatal Cohort longitudinal study demonstrated that delayed acquisition of motoric milestones, including sitting and walking, was correlated with later onset of adult schizophrenia [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. These findings highlight the importance of monitoring developmental milestones during childhood to identify individuals at risk for future psychopathological comorbidities.\u003c/p\u003e \u003cp\u003eDespite these findings, research on the association between developmental milestones and core features of TS remains limited. A notable study by Comings and Comings (1987) found no significant delays in walking or talking among individuals with TS compared to controls; however, there was a significant delay in toilet training in most TS patients. This study did not take into account tic severity or psychopathological comorbidities [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. More recent studies have shown that developmental delays are more common in individuals with both TS and psychopathological comorbidities, such as ADHD, compared to those with TS alone [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eGiven the limited research, the connection between developmental delays and later-life tic severity and psychopathological comorbidities remains inconclusive. To address this gap, we retrospectively examined early developmental milestones in a large sample of youth (ages 3–16) with chronic tics from the European Multicenter Tics in Children Study (EMTICS) [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Our study aimed to investigate the developmental milestones of individuals with chronic CTDs. Specifically, we sought to explore the relationship between the age of acquiring early developmental milestones (motor, language, and toilet training) and both tic severity and impairment, as well as psychopathological comorbidities, including OCD, ADHD, ODD, and suspected ASD. We hypothesized that delayed acquisition of these milestones would predict greater tic severity and impairment, along with more severe comorbid symptoms or higher rates of comorbid psychopathologies.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e\u003c/p\u003e\n\n "},{"header":"Methods","content":"\u003ch3\u003eParticipants and Procedure\u003c/h3\u003e\u003cp\u003eThe sample included 383 children and adolescents aged 3 to 16 years with Tourette syndrome (TS) or chronic tic disorder (CTD) who participated in the baseline assessment of the EMTICS study, which investigates the role of genetic, autoimmune, and psychosocial factors in the onset and progression of tics [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Participants were recruited from sixteen child mental health or pediatric neurology outpatient clinics across Europe and Israel, as well as through advertisements directed at patient organizations and health professionals. All participants who met the diagnostic criteria for TS or CTD according to the DSM-IV-TR (American Psychiatric Association) were invited, along with their parents or guardians, to participate in the study [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eInclusion criteria required participants to be between 3 and 16 years old, with a confirmed diagnosis of TS or CTD based on DSM-IV-TR criteria [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Additionally, for the current study, only participants whose parents had completed all questions related to early developmental milestones were included. Exclusion criteria included severe medical or neurological illness, recent antibiotic treatment within the past month, or inability to comply with study procedures. Written informed consent was obtained from parents or legal guardians, and participating adolescents provided either written assent or consent, depending on local medical-ethical regulations. Ethical approval was granted by the relevant Research Ethics Committees at each participating center.\u003c/p\u003e\u003cp\u003eBaseline measures, including parent-reported questionnaires and a clinical interview, were collected during the initial EMTICS visit. Additionally, a clinician confirmed the diagnosis of TS or CTD and assessed for ADHD and OCD according to DSM-IV-TR criteria [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e\u003ch2\u003eMeasures\u003c/h2\u003e\u003cp\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eDemographic information\u003c/span\u003e, including the child's sex, age at evaluation, study site, and ethnicity, was collected through a demographic questionnaire .\u003c/p\u003e\u003cp\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eEarly Developmental Milestones\u003c/span\u003e were gathered using the Modified Schedule for Risk and Protective Factors in Early Development (MSRPFED) [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Parents reported the age (in months) at which their child acquired eight developmental milestones from early life: sitting, walking, first words, sentence completion, daytime and nighttime bladder control, and bowel control. This information created eight continuous developmental measures for analysis. Developmental delays were assessed using the Denver II assessment for motor and language development [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], with suspected delays determined using the 90th percentile age norms. Toilet training and delays differentiated by sex were assessed based on the 75th percentile, following the methodology of Schum et al. [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Consequently, an additional dichotomous variable was created for each developmental milestone to identify children with developmental delays.\u003c/p\u003e\u003cp\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eTic severity and impairment\u003c/span\u003e symptoms were measured using the clinician-rated \u003cem\u003eYale Global Tic Severity Scale\u003c/em\u003e (YGTSS) [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Each of the following dimensions was rated on a five-point scale: number, frequency, intensity, interference, and complexity over the past week. Scores were calculated for motor tic severity (range: 0–25), vocal tic severity (range: 0–25), total tic severity (range: 0–50), and the tic impairment score (subjective evaluation of impairment caused by tics, range: 0–50). In the current study, Cronbach’s alpha values were calculated as follows: α = .88 for the total tic severity scale, α = .82 for the motor subscale, and α = .89 for the vocal subscale. Total tic severity cut-offs were defined as follows: minimal tics \u0026lt; 10, mild tics: 10–20, moderate tics: 20–40, and severe tics: 40–50, based on the work of Leckman and colleagues [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eObsessive-Compulsive Disorder (OCD)\u003c/span\u003e symptoms were assessed using the clinician-rated Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e], which evaluates five dimensions: time, interference, distress, resistance, and control associated with obsessions and compulsions over the past week. Each dimension is rated on a five-point scale. The scale provides three summary scores: obsession severity (ranging from 0 to 20; α = .92), compulsion severity (ranging from 0 to 20; α = .93), and total OCD severity (ranging from 0 to 40; α = .94). A dichotomous diagnosis of OCD was based on DSM-IV-TR criteria, as determined by a trained clinician, or a CY-BOCS total severity score of 16 or higher, following the cut-off established by Scahill et al. [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eAttention Deficit/Hyperactivity Disorder (ADHD)\u003c/span\u003e symptoms were assessed using the abbreviated version of \u003cem\u003ethe Swanson, Nolan, and Pelham, version IV (SNAP-IV)\u003c/em\u003e rating scale, which evaluates symptoms over the past week on a four-point scale. This scale yields three scores: inattention score (9 items, range 0–27; current study α = .91), hyperactivity-impulsivity score (9 items, range 0–27; α = .90), and combined score (18 items, range 0–54; current study α = .94), with higher scores indicating greater symptom severity [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. A dichotomous diagnosis of ADHD was determined based on DSM-IV-TR criteria, as diagnosed by a trained clinician, and included any of the ADHD subtypes (inattentive, hyperactive, or combined) [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eOppositional Defiant Disorder (ODD)\u003c/span\u003e symptoms were assessed using the parent-rated \u003cem\u003eSwanson, Nolan, and Pelham, version IV\u003c/em\u003e (SNAP-IV) abbreviated version rating scale. ODD symptoms were evaluated over the past week on a four-point scale, with higher scores indicating greater symptom severity (8 items, range 0–24; current study α = .91). A dichotomous ODD variable was defined as scoring above the 95th percentile cut-off on the SNAP-IV questionnaire (ODD mean score ≥ 1.88) [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eSuspected Autism Spectrum Disorder (ASD)\u003c/span\u003e symptoms were assessed using the parent-rated Autism Spectrum Screening Questionnaire (ASSQ) [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. A three-point scale was employed to evaluate symptoms across four domains: social interaction, communication, restricted and repetitive behaviors, and motor clumsiness, along with other associated symptoms. Higher scores indicated greater suspected ASD symptom severity (27 items, range 0–54; α = .90). A dichotomous variable for suspected ASD was defined as scoring above the established cut-off (ASSQ score ≥ 19) [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eMissing data patterns were examined using Little's MCAR (Missing Completely at Random) test, incorporating variables such as developmental milestones, tics, OCD, ADHD, ODD, suspected ASD, sex, age at visit, ethnicity, and site.\u003c/p\u003e\u003cp\u003eA correlation matrix was created to assess the relationships between early developmental milestones, tic severity and impairment, and the severity of psychopathological comorbidity symptoms (all continuous variables).\u003c/p\u003e\u003cp\u003eDue to the weak correlations with continuous variables, we proceeded with our analysis using dichotomous dependent variables for ADHD, OCD, and ODD (based on DSM-IV-TR criteria or established cut-offs from gold standard report measures).\u003c/p\u003e\u003cp\u003eTo evaluate whether developmental milestones are related to the presence of psychopathological comorbid diagnoses, logistic regression analyses were performed separately for each diagnosis, with the presence of ADHD, ODD, OCD, and suspected ASD as dependent variables (0 = without the respective comorbidity; 1 = with the respective comorbidity). Independent variables included the age in months for each developmental milestone (sitting, walking, first words, sentence completion, daytime/nighttime bladder control, and bowel control). Covariates such as sex, age, and site were also included.\u003c/p\u003e\u003cp\u003eResults were reported using odds ratios (OR), where OR values below, equal to, or above 1 reflect lower, neutral, or higher odds of the outcome, respectively. Model accuracy was evaluated using a classification table to compare observed and predicted outcomes. All analyses were conducted using IBM SPSS, Version 20.0 [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e], with a significance level of α = .05.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec6\"\u003e\n \u003ch2\u003eSample characteristics\u003c/h2\u003e\n \u003cp\u003eThe initial sample consisted of 709 participants. Only participants whose parents had completed all questions related to early developmental milestones were included. Missing data were assessed using Little\u0026apos;s MCAR test (considering variables such as sex, age at visit, ethnicity, study site, tics, OCD, ADHD, ODD, and suspected ASD), which indicated that the missing data were completely random (\u0026chi;\u0026sup2;(523)\u0026thinsp;=\u0026thinsp;564.26, p\u0026thinsp;=\u0026thinsp;.10). To validate this result, differences in outcome variables between participants with complete data and those who were excluded were examined using t-tests. Although significant differences were found for nighttime bowel control and ADHD (with higher scores for excluded participants), the effect sizes were relatively small (Cohen\u0026apos;s d\u0026thinsp;\u0026le;\u0026thinsp;.2). The final sample included 383 participants.\u003c/p\u003e\n \u003cp\u003eThe majority of participants (87.5%, n\u0026thinsp;=\u0026thinsp;335) were diagnosed with Tourette syndrome (TS), 11.5% (n\u0026thinsp;=\u0026thinsp;44) with chronic motor tic disorder, and less than 1% (n\u0026thinsp;=\u0026thinsp;1; 0.3%) with chronic vocal tic disorder. In terms of tic severity, 47% (n\u0026thinsp;=\u0026thinsp;180) of participants exhibited moderate tic severity, 36% (n\u0026thinsp;=\u0026thinsp;138) had mild tics, 16.2% (n\u0026thinsp;=\u0026thinsp;62) had minimal tics, and 0.8% (n\u0026thinsp;=\u0026thinsp;3) had severe tics. Descriptive statistics for demographics, tic severity, impairment, and comorbid psychopathology symptoms are presented in Table \u003cspan\u003e1\u003c/span\u003e.\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 1\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003e\u003cem\u003eDemographics and clinical characteristics (n\u0026thinsp;=\u0026thinsp;383)\u003c/em\u003e\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"3\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eM\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eN (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRange\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e10.67\u0026thinsp;\u0026plusmn;\u0026thinsp;2.69\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.35\u0026ndash;16.79\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex (male)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e294 (76.8)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eEthnicity (Caucasian)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e362 (94.5)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChronic tic disorder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMotor tic severity score\u003csup\u003e\u003cem\u003ea\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.42\u0026thinsp;\u003cstrong\u003e\u0026plusmn;\u003c/strong\u003e\u0026thinsp;4.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u0026ndash;23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVocal tic severity score\u003csup\u003e\u003cem\u003ea\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.40\u0026thinsp;\u003cstrong\u003e\u0026plusmn;\u003c/strong\u003e\u0026thinsp;5.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u0026ndash;22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal tic severity score\u003csup\u003e\u003cem\u003ea\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.81\u0026thinsp;\u003cstrong\u003e\u0026plusmn;\u003c/strong\u003e\u0026thinsp;8.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u0026ndash;44\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTic impairment score\u003csup\u003e\u003cem\u003ea\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.73\u0026thinsp;\u003cstrong\u003e\u0026plusmn;\u003c/strong\u003e\u0026thinsp;11.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u0026ndash;50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eOCD\u003c/strong\u003e\u003csup\u003e\u003cem\u003eb\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e121 (31)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eObsessions severity score\u003csup\u003e\u003cem\u003eb\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.20\u0026thinsp;\u003cstrong\u003e\u0026plusmn;\u003c/strong\u003e\u0026thinsp;4.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u0026ndash;17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCompulsions severity score\u003csup\u003e\u003cem\u003eb\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.85\u0026thinsp;\u003cstrong\u003e\u0026plusmn;\u003c/strong\u003e\u0026thinsp;4.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u0026ndash;20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal OCD severity score\u003csup\u003e\u003cem\u003eb\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.04\u0026thinsp;\u003cstrong\u003e\u0026plusmn;\u003c/strong\u003e\u0026thinsp;8.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u0026ndash;34\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eADHD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e96 (25.1)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eInattention severity score\u003csup\u003e\u003cem\u003ec\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.59\u0026thinsp;\u003cstrong\u003e\u0026plusmn;\u003c/strong\u003e\u0026thinsp;6.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u0026ndash;27\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHyperactivity severity score\u003csup\u003e\u003cem\u003ec\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.87\u0026thinsp;\u003cstrong\u003e\u0026plusmn;\u003c/strong\u003e\u0026thinsp;6.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u0026ndash;27\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCombined severity score\u003csup\u003e\u003cem\u003ec\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.46\u0026thinsp;\u003cstrong\u003e\u0026plusmn;\u003c/strong\u003e\u0026thinsp;12.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u0026ndash;54\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eODD\u003c/strong\u003e\u003csup\u003e\u003cem\u003ec\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eODD severity score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.23\u0026thinsp;\u003cstrong\u003e\u0026plusmn;\u003c/strong\u003e\u0026thinsp;5.96\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e49 (12.8)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u0026ndash;24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSuspected ASD\u003c/strong\u003e\u003csup\u003e\u003cem\u003ed\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.06\u0026thinsp;\u003cstrong\u003e\u0026plusmn;\u003c/strong\u003e\u0026thinsp;8.93\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e72 (18.8)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u0026ndash;46\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSuspected ASD severity score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003e64 (16.7)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e\u003cem\u003eAbbreviations:\u003c/em\u003e\u0026nbsp; \u0026nbsp;\u003cem\u003eOCD, Obsessive Compulsive Disorder; ADHD, Attention Deficit Hyperactive Disorder; ODD, Oppositional Defiant Disorder; suspected ASD, suspected Autism Spectrum Disorder;\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u003csup\u003ea\u003c/sup\u003e\u003c/em\u003e\u003cem\u003eby YGTSS \u0026ndash; Yale Global Tic Severity Scale; \u003csup\u003eb\u003c/sup\u003eby CYBOCS \u0026ndash; Children\u0026rsquo;s Yale-Brown Obsessive Compulsive Scale; \u003csup\u003ec\u003c/sup\u003eby SNAP \u0026ndash; Swanson, Nolan and Pelham; \u003csup\u003ed\u003c/sup\u003e by ASSQ \u0026ndash; Autism Spectrum Screening Questionnaire.\u003c/em\u003e\u003c/p\u003e\n \u003ch2\u003e\u003cem\u003eEarly developmental milestones\u0026nbsp;\u003c/em\u003e\u003c/h2\u003e\n \u003cp\u003eTable 2 presents the average age at which participants achieved early developmental milestones, as well as the percentage of participants with suspected delays. Daytime and nighttime bowel control were highly correlated (r = .83, p \u0026lt; .01) and were therefore combined into a single variable for further analysis based on clinical considerations. Table 3 shows inter-correlations between developmental milestones, with significant positive correlations within each domain (motor, language, and toilet training; r = .39\u0026ndash;.67, p \u0026lt; .01). Cross-domain correlations ranged from minor to moderate positive (r = .02\u0026ndash;.46, p = n.s.\u0026ndash;\u0026lt; .01).\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 2\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003e\u003cem\u003eAge of acquiring early developmental milestones (n\u0026thinsp;=\u0026thinsp;383)\u003c/em\u003e\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"5\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDevelopmental milestones\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMd\u003c/p\u003e\n \u003cp\u003e(months)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eM\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003cp\u003e(months)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRange\u003c/p\u003e\n \u003cp\u003e(months)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSuspected developmental delay\u003c/p\u003e\n \u003cp\u003e% (n)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMotor development\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSitting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.84\u0026thinsp;\u003cstrong\u003e\u0026plusmn;\u003c/strong\u003e\u0026thinsp;1.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u0026ndash;12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.9 (11)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWalking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.01\u0026thinsp;\u003cstrong\u003e\u0026plusmn;\u003c/strong\u003e\u0026thinsp;2.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.5\u0026ndash;36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.1 (31)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eLanguage development\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFirst words\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.28\u0026thinsp;\u003cstrong\u003e\u0026plusmn;\u003c/strong\u003e\u0026thinsp;5.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u0026ndash;52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.8 (76)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eComplete a sentence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21.95\u0026thinsp;\u003cstrong\u003e\u0026plusmn;\u003c/strong\u003e\u0026thinsp;7.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8\u0026ndash;60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18.3 (70)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eToilet training\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDay bladder control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30.80\u0026thinsp;\u003cstrong\u003e\u0026plusmn;\u003c/strong\u003e\u0026thinsp;13.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u0026ndash;168\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.9 (34)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNight bladder control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37.34\u0026thinsp;\u003cstrong\u003e\u0026plusmn;\u003c/strong\u003e\u0026thinsp;21.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12\u0026ndash;192\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.1 (73)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBowel control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31.85\u0026thinsp;\u003cstrong\u003e\u0026plusmn;\u003c/strong\u003e\u0026thinsp;10.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12\u0026ndash;134\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15.4 (59)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"5\"\u003e\n \u003cp\u003e\u003csup\u003e\u003cem\u003ea\u003c/em\u003e\u003c/sup\u003e\u003cem\u003eAccording to The Denver II Developmental Screening Test (1992)\u003c/em\u003e [\u003cspan\u003e28\u003c/span\u003e].\u003c/p\u003e\n \u003cp\u003e\u003csup\u003e\u003cem\u003eb\u003c/em\u003e\u003c/sup\u003e\u003cem\u003eAccording to Schum, et al (2002)\u003c/em\u003e [\u003cspan\u003e29\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 3\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003e\u003cem\u003eCorrelation matrix of intra-correlations between early developmental milestones (n\u0026thinsp;=\u0026thinsp;383)\u003c/em\u003e\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"9\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDomain\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDevelopmental milestones\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eWalking\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eFirst words\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eComplete a sentence\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDay bladder control\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNight bladder control\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBowel control\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eMotor\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSitting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.40**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.22**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.16**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWalking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.46**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.28**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.14**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eLanguage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFirst words\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.68**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e.12*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.25**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eComplete a sentence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.22**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003e\u003cstrong\u003eToilet training\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDay bladder control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.67**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.59**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNight bladder control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.46**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBowel control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"9\"\u003e\n \u003cp\u003e\u003cem\u003e* p\u0026thinsp;\u0026lt;\u0026thinsp;.05, ** p\u0026thinsp;\u0026lt;\u0026thinsp;.01\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003ch2\u003e\u003cem\u003eCorrelations between early acquisition of developmental milestones, tics, and comorbid symptoms\u003c/em\u003e\u003c/h2\u003e\n \u003cp\u003eA Pearson correlation analysis (Table 4) revealed weak correlations overall, with small effect sizes (r \u0026lt; .21). Notably, the acquisition of sitting was not associated with any comorbid psychopathological symptoms. Motor tics and tic impairment were correlated with walking (r = .11\u0026ndash;.12), while vocal tics were correlated with first words (r = .12). OCD showed correlations with walking, first words, and sentence completion (r = .12\u0026ndash;.18). ADHD was correlated with walking, first words, sentence completion, and bowel control (r = .12\u0026ndash;.21). ODD was correlated with first words (r = .15), and suspected ASD was correlated with bladder and bowel control (r = .10\u0026ndash;.17). \u003cspan dir=\"RTL\"\u003eתחתית הטופס\u003c/span\u003e\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 4\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003e\u003cem\u003eCorrelation matrix between early developmental milestones and severity of tics and comorbid psychopathology symptoms (n\u0026thinsp;=\u0026thinsp;383)\u003c/em\u003e\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"8\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"7\"\u003e\n \u003cp\u003eAge of acquiring early developmental milestones (months)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSitting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWalking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFirst words\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eComplete a sentence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDay bladder control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNight bladder control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBowel control\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTics\u003c/strong\u003e\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMotor tic severity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026minus;\u0026thinsp;.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.11*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026minus;\u0026thinsp;.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVocal tic severity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026minus;\u0026thinsp;.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.12*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026minus;\u0026thinsp;.007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal tic severity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026minus;\u0026thinsp;.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026minus;\u0026thinsp;.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eImpairment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026minus;\u0026thinsp;.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.12*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.09\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eOCD severity\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003eb\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eObsessions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.16**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.15**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.12**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026minus;\u0026thinsp;.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCompulsions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.17**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026minus;\u0026thinsp;.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal OCD severity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.0\u003cem\u003e1\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.18**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.12*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.11*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026minus;\u0026thinsp;.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eADHD severity\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003ec\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eInattention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.18**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.18**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.13*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.1*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHyperactivity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.16**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.21**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.12*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.11*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCombined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.19**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.21**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.13**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.12*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eODD severity\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003ec\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026minus;\u0026thinsp;.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.15**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026minus;\u0026thinsp;.008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026minus;\u0026thinsp;.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eASD severity\u003c/strong\u003e\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.17**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.17**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.10*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"8\"\u003e\n \u003cp\u003e\u003cem\u003e* p\u0026thinsp;\u0026lt;\u0026thinsp;.05, ** p\u0026thinsp;\u0026lt;\u0026thinsp;.01\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eAbbreviations: OCD, Obsessive Compulsive Disorder; ADHD, Attention Deficit Hyperactive Disorder; suspected ASD, suspected Autism Spectrum Disorder; ODD, Oppositional Defiant Disorder.\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003csup\u003e\u003cem\u003ea\u003c/em\u003e\u003c/sup\u003e\u003cem\u003eby YGTSS \u0026ndash; Yale Global Tic Severity Scale;\u003c/em\u003e \u003csup\u003e\u003cem\u003eb\u003c/em\u003e\u003c/sup\u003e\u003cem\u003eby CYBOCS \u0026ndash; Children\u0026rsquo;s Yale-Brown Obsessive Compulsive Scale;\u003c/em\u003e \u003csup\u003e\u003cem\u003ec\u003c/em\u003e\u003c/sup\u003e\u003cem\u003eby SNAP \u0026ndash; Swanson, Nolan and Pelham;\u003c/em\u003e \u003csup\u003e\u003cem\u003ed\u003c/em\u003e\u003c/sup\u003e \u003cem\u003eby ASSQ \u0026ndash; Autism Spectrum Screening Questionnaire.\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003ch2\u003e\u003cem\u003ePrediction of psychopathological comorbidity diagnoses by early developmental milestones\u003c/em\u003e\u003c/h2\u003e\n \u003cp\u003eLogistic regression analyses were conducted to explore the relationship between early developmental milestones and comorbid psychopathological diagnoses\u0026nbsp;(Table 5), with the results detailed below. Unless otherwise noted, the covariates (sex, age, and site) were not significant\u003c/p\u003e\n \u003cp\u003e\u003cu\u003eOCD\u003c/u\u003e: The model was significant (\u0026chi;\u0026sup2;(10) = 34.2, p \u0026lt; .01), accounting for 12.2% of the variance in OCD and correctly classifying 68.7% of cases. Later acquisition of walking (OR = 1.13; 1.01\u0026ndash;1.27, p \u0026lt; .05) and the child\u0026apos;s older age (covariate) (OR = 1.16; 1.06\u0026ndash;1.26, p \u0026lt; .01) increased the likelihood of an OCD diagnosis.\u003c/p\u003e\n \u003cp\u003e\u003cu\u003eADHD\u003c/u\u003e: The model predicting ADHD was also significant (\u0026chi;\u0026sup2;(10) = 22.97, p \u0026lt; .01), accounting for 8.6% of the variance and correctly classifying 75% of cases. Later acquisition of first words increased the likelihood of an ADHD diagnosis (OR = 1.06; 1.00\u0026ndash;1.30, p \u0026lt; .05), while later acquisition of sentence completion reduced the likelihood (OR = 0.95; 0.91\u0026ndash;0.99, p \u0026lt; .05).\u003c/p\u003e\n \u003cp\u003e\u003cu\u003eODD\u003c/u\u003e: Significant results were found (\u0026chi;\u0026sup2;(10) = 25.11, p \u0026lt; .05), contributing 11.9% to the variance in ODD and correctly classifying 87.2% of cases. Later acquisition of first words increased the likelihood of ODD (OR = 1.13; 1.04\u0026ndash;1.22, p \u0026lt; .01), while later acquisition of sitting reduced the likelihood (OR = 0.70; 0.54\u0026ndash;0.90, p \u0026lt; .01). Being male (covariate) also increased the likelihood of an ODD diagnosis (OR = 0.36; 0.14\u0026ndash;0.90, p \u0026lt; .03).\u003c/p\u003e\n \u003cp\u003e\u003cu\u003eSuspected ASD\u003c/u\u003e: The model was significant (\u0026chi;\u0026sup2;(10) = 34.32, p \u0026lt; .01), accounting for 13.8% of the variance in suspected ASD and correctly classifying 81.2% of cases. Later acquisition of first words increased the likelihood of suspected ASD (OR = 1.13; 1.05\u0026ndash;1.21, p \u0026lt; .01), while sentence completion reduced the likelihood (OR = 0.95; 0.89\u0026ndash;1.00, p \u0026lt; .05).\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab5\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 5\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003e\u003cem\u003eLogistic Regressions for predicting comorbid psychopathology diagnoses by early developmental milestones\u003c/em\u003e\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"8\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePrediction of OCD by:\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSE\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eWald\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eExp(B) (95% C.I)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eNagelkerkeR\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOverall\u003c/p\u003e\n \u003cp\u003eSitting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026minus;\u0026thinsp;.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.92 (.78\u0026ndash;1.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" rowspan=\"7\"\u003e\n \u003cp\u003e.122\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWalking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.13 (1.01\u0026ndash;1.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFirst words\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.04 (.98\u0026ndash;1.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eComplete sentence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00 (.96\u0026ndash;1.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDay bladder control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.02 (.99\u0026ndash;1.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNight bladder control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026minus;\u0026thinsp;.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.99 (.97\u0026ndash;1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBowel control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.01 (.98\u0026ndash;1.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrediction of ADHD by\u003c/strong\u003e:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWald\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eExp(B) (95% C.I)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eNagelkerkeR\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOverall\u003c/p\u003e\n \u003cp\u003eSitting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026minus;\u0026thinsp;.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.97 (.82\u0026ndash;1.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" rowspan=\"7\"\u003e\n \u003cp\u003e.086\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWalking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.12 (1.00\u0026ndash;1.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFirst words\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.06 (1.00\u0026ndash;1.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eComplete sentence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026minus;\u0026thinsp;.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.95 (.91\u0026ndash;1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDay bladder control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026minus;\u0026thinsp;.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.98 (.93\u0026ndash;1.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNight bladder control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00 (.98\u0026ndash;1.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBowel control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.05 (.98\u0026ndash;1.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrediction of suspected ASD by\u003c/strong\u003e:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWald\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eExp(B) (95% C.I)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eNagelkerkeR\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOverall\u003c/p\u003e\n \u003cp\u003eSitting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.086\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.05 (.87\u0026ndash;1.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" rowspan=\"7\"\u003e\n \u003cp\u003e.138\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWalking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026minus;\u0026thinsp;.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.91 (.80\u0026ndash;1.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFirst words\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.13 (1.05\u0026ndash;1.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eComplete sentence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026minus;\u0026thinsp;.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.95 (.89\u0026ndash;1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDay bladder control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.01 (.98\u0026ndash;1.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNight bladder control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.01 (1.00\u0026ndash;1.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBowel control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026minus;\u0026thinsp;.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.99 (.96\u0026ndash;1.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrediction of ODD by\u003c/strong\u003e:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWald\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eExp(B) (95% C.I)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eNagelkerkeR\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOverall\u003c/p\u003e\n \u003cp\u003eSitting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026minus;\u0026thinsp;.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.70 (.54 \u0026ndash; .90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e.119\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWalking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.07 (.94\u0026ndash;1.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFirst words\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.12 (1.04\u0026ndash;1.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eComplete sentence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026minus;\u0026thinsp;.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.94 (.88\u0026ndash;1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDay bladder control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026minus;\u0026thinsp;.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.96 (.88\u0026ndash;1.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNight bladder control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00 (.98\u0026ndash;1.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBowel control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.1.02 (.94\u0026ndash;1.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"7\"\u003e\n \u003cp\u003e\u003cem\u003eNote: the models covaried sex site and age (significant results are presented in the main text).\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eAbbreviations: ADHD, Attention Deficit Hyperactive Disorder; OCD, Obsessive Compulsive Disorder; suspected ASD, suspected Autism Spectrum Disorder; ODD, Oppositional Defiant Disorder.\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe current study included a large sample of children and adolescents\u0026nbsp;aged 3\u0026ndash;16 years with chronic tic disorders (CTD), aimed to explore the relationship between delayed acquisition of key developmental milestones (motor, language, and toilet training) and tic severity,\u0026nbsp;tic-related\u0026nbsp;impairment as well as psychopathological\u0026nbsp;comorbidities. The primary finding was that delayed language acquisition, particularly speaking first words in infancy, predicted later psychopathological\u0026nbsp;comorbidities associated with CTD, including OCD, ADHD, ODD and suspected ASD.\u003c/p\u003e\n\u003cp\u003eIn line with our hypothesis, tic severity and impairment were correlated with developmental milestones albeit with small effect size. Interestingly, motor tics and tic impairment were associated with the age of first walking, while vocal tics were linked to delayed acquisition of first words. Similarly, Cravedi et al., (2018), identified developmental delays in children with tics and neurodevelopmental comorbidities, however, their study categorized TS individuals into clusters rather than using continuous measures\u0026nbsp;[15]. In contrast, Coming and Comings (1987), in a different study design, found no significant delays in talking or walking among TS patients compared to controls, but reported significant delays in bladder and bowel control\u0026nbsp;[32]. These methodological differences may explain the variance in findings between studies. Thus, further research is needed to draw definitive conclusions.\u003c/p\u003e\n\u003cp\u003eRegarding related psychopathological comorbidities, our findings revealed a correlation between OCD, both severity and diagnosis, and delays in motor (walking) and language development. This aligns with previous research indicating that children with anxiety, a common comorbidity of OCD, often experience developmental delays in motor, language, and toilet training milestones\u0026nbsp;[20, 33, 34]\u0026nbsp;Importantly, this study focused on tic-related OCD, and future research should further explore developmental delays in cases of non-tic-related OCD\u0026nbsp;[35, 36].\u003c/p\u003e\n\u003cp\u003eOur findings corroborate previous research that links neurodevelopmental disorders to developmental delays\u0026nbsp;[14, 37, 38]. Specifically, we found that delayed language acquisition and bowel control were both associated with the severity of ADHD and suspected ASD symptoms. This aligns with LeBeau et al. (2022), who reported that bowel control difficulties were linked to the severity of ADHD and ASD symptoms, while delayed speech acquisition predicted later ASD diagnoses\u0026nbsp;[11]. Similarly, Gurevitz et al. (2012) identified language delay as a significant early predictor of ADHD\u0026nbsp;[39, 40].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Regarding ODD, our study found a significant correlation between delayed acquisition of first words and later ODD diagnosis and severity of symptoms . This aligns with previous research showing that children with ODD often experience slower language development and less speech clarity [22].\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003eNevertheless more studies on ODD with or without TS are needed.\u003c/p\u003e\n\u003cp\u003eInterestingly, negative correlations were found between ADHD and suspected ASD diagnoses with sentence completion, as well as between ODD diagnoses and sitting. One possible explanation is that children with psychopathological comorbidities often exhibit highly variable developmental trajectories, resulting in uneven progress across different developmental domains. For example, LeBeau et al. (2022) identified a similar pattern, particularly noting negative correlations between ADHD and delayed language acquisition [11]. Another explanation may lie in the tendency of parents to more easily recall prominent milestones, such as first words or walking, compared to less noticeable ones like sentence completion or sitting. This highlights the potential influence of memory bias in parental reporting of developmental milestones.\u003c/p\u003e\n\u003cp\u003eThis study highlights the association between early developmental delays, including language, motor acquisition, and bowel/bladder control, and the later development of psychopathological comorbidities (OCD, ADHD, ODD, and suspected ASD) in CTD patients. Identifying these relationships could improve early detection of at-risk individuals and facilitate timely, tailored interventions, potentially improving long-term outcomes and quality of life for CTD patients with comorbid psychopathologies. Furthermore, our findings underscore the importance of distinguishing between patients with tics alone and those with both tics and comorbid psychopathologies, as demonstrated in previous studies Top of Form[3, 6, 40]. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStrengths and Limitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWhile this study benefited from a substantial sample size, several limitations should be considered. First, most participants were recruited from clinics, which may have introduced selection bias, resulting in a higher proportion of individuals with psychopathological comorbidities compared to the general population. Second, the assessment of developmental delays was retrospective and relied on parental reports, potentially introducing memory bias\u0026nbsp;[41]. Third, given the challenge of establishing universally applicable developmental norms, we relied on commonly accepted norms from validated assessment tools used in child developmental centers. Additionally, the absence of a healthy control group and a group with similar psychopathological comorbidities but without tics limits our ability to make broader comparisons. Finally, the potential impact of multiple comparisons on the results should be acknowledged. However, the consistency of patterns across our statistical analyses, particularly concerning language delays and their relationship with symptom severity, supports the robustness of our findings. Future studies should adopt a prospective design with a healthy control group and long-term follow-up from infancy to minimize recall bias and provide a more comprehensive understanding of the relationship between developmental milestones and psychopathological comorbidities.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgement \u0026amp; Funding:\u0026nbsp;\u003c/strong\u003eThe authors are deeply grateful to all the children and their parents who willingly participated to make this research possible. The longitudinal European Multicenter Tics in Children Study (EMTICS) has received funding from the European Union\u0026rsquo;s Seventh Framework Program for research, technological development, and demonstration under Grant agreement no. 278367. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclarations of Interest:\u003c/strong\u003e None\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eDiagnostic and statistical manual of mental disorders: DSM-5\u003csup\u003eTM\u003c/sup\u003e, 5th ed. American Psychiatric Publishing, Inc., Arlington, VA, US\u003c/li\u003e\n\u003cli\u003eBloch MH, Leckman JF (2009) Clinical course of Tourette syndrome. Journal of Psychosomatic Research 67:497\u0026ndash;501. https://doi.org/10.1016/j.jpsychores.2009.09.002\u003c/li\u003e\n\u003cli\u003eHirschtritt ME, Lee PC, Pauls DL, et al (2015) Lifetime Prevalence, Age of Risk, and Genetic Relationships of Comorbid Psychiatric Disorders in Tourette Syndrome. 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Mol Psychiatry 26:1224\u0026ndash;1233. https://doi.org/10.1038/s41380-019-0532-z\u003c/li\u003e\n\u003cli\u003eLeckman JF, Denys D, Simpson HB, et al (2010) Obsessive\u0026ndash;compulsive disorder: a review of the diagnostic criteria and possible subtypes and dimensional specifiers for DSM-V. Depression and Anxiety 27:507\u0026ndash;527. https://doi.org/10.1002/da.20669\u003c/li\u003e\n\u003cli\u003eFlensborg-Madsen T, Mortensen EL (2018) Associations of Early Developmental Milestones With Adult Intelligence. Child Development 89:638\u0026ndash;648. https://doi.org/10.1111/cdev.12760\u003c/li\u003e\n\u003cli\u003ePerna R, Loughan A (2012) Early Developmental Delays: Neuropsychological Sequelae and Subsequent Diagnoses. Applied Neuropsychology: Child 1:57\u0026ndash;62. https://doi.org/10.1080/09084282.2011.643963\u003c/li\u003e\n\u003cli\u003eGurevitz M, Geva R, Varon M, Leitner Y (2014) Early Markers in Infants and Toddlers for Development of ADHD. J Atten Disord 18:14\u0026ndash;22. https://doi.org/10.1177/1087054712447858\u003c/li\u003e\n\u003cli\u003eMathews CA, Grados MA (2011) Familiality of Tourette Syndrome, Obsessive-Compulsive Disorder, and Attention-Deficit/Hyperactivity Disorder: Heritability Analysis in a Large Sib-Pair Sample. Journal of the American Academy of Child \u0026amp; Adolescent Psychiatry 50:46\u0026ndash;54. https://doi.org/10.1016/j.jaac.2010.10.004\u003c/li\u003e\n\u003cli\u003eTanur JM (1992) Questions About Questions: Inquiries into the Cognitive Bases of Surveys. Russell Sage Foundation\u003cstrong\u003e\u003cu\u003e\u003c/u\u003e\u003c/strong\u003e\u003c/li\u003e\n\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":"Developmental milestones, Tourette syndrome, Tic disorders, attention deficit disorder, (ADHD), Obsessive compulsive disorder (OCD)","lastPublishedDoi":"10.21203/rs.3.rs-5368250/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5368250/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eChronic Tic disorders (CTD) including Tourette Syndrome (TS), are associated with psychopathological comorbidities. Attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and other comorbidities have been linked to delays in early developmental milestones. Few studies have investigated the relationship between early developmental milestones, tic severity, and related comorbidities.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e383 participants aged 3\u0026ndash;16 years (76.8%, n\u0026thinsp;=\u0026thinsp;294 boys) with CTD from the baseline assessment of the \u003cem\u003eEuropean Multicenter Tics in Children Study\u003c/em\u003e (EMTICS), were evaluated for early developmental milestones (sitting, walking, first words, complete a sentence, bladder and bowel control), tic severity, tic-related functional impairment, obsessive-compulsive disorder (OCD), ADHD, oppositional defiant disorder (ODD) and suspected ASD. Data was collected using gold-standard self and clinician reporting instruments. Analyses included Pearson correlations and logistic regressions.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eCorrelations between the acquisition of developmental milestones and tic severity or impairment were significant with small effect sizes (severity of motor tics and tic impairment were correlated with walking (r\u0026thinsp;=\u0026thinsp;.11), while vocal tics were correlated with first words (r\u0026thinsp;=\u0026thinsp;.12)). Logistic regression revealed that delayed acquisition of first words was significantly associated with ADHD, ODD and suspected ASD (Odds Ratio (ROR): 1-1.13, 1.05\u0026ndash;1.21, 1.01\u0026ndash;1.16, 1.04\u0026ndash;1.22, respectively), while delayed walking acquisition was associated with OCD (ROR: 1.01\u0026ndash;1.27).\u003c/p\u003e\u003ch2\u003eDiscussion\u003c/h2\u003e \u003cp\u003eThis study highlights the association between early developmental milestones and later psychopathological comorbidities in CTD patients. These findings emphasize the need for further research to distinguish between children with only tics and those with tics and psychopathological comorbidities, to improve early detection of individuals at risk.\u003c/p\u003e","manuscriptTitle":"Early developmental milestones associated with tics and psychopathological comorbidity : An EMTICS study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-14 06:21:15","doi":"10.21203/rs.3.rs-5368250/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-01-05T15:56:03+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-12-28T11:34:10+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-12-15T18:14:15+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-12-01T23:33:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"54331954996963540746589647556584895230","date":"2024-11-29T22:20:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"270705205787908487945082315958386261881","date":"2024-11-29T09:02:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"172537067472970613567831332384719460438","date":"2024-11-25T18:10:24+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-11-24T15:38:12+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-11-22T08:07:20+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-11-02T03:04:07+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Child \u0026 Adolescent Psychiatry","date":"2024-10-31T16:33:07+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":"5d0e265c-738a-4b37-a899-579a3cf164b6","owner":[],"postedDate":"November 14th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-08-07T07:12:17+00:00","versionOfRecord":{"articleIdentity":"rs-5368250","link":"https://doi.org/10.1007/s00787-025-02807-5","journal":{"identity":"european-child-and-adolescent-psychiatry","isVorOnly":false,"title":"European Child \u0026 Adolescent Psychiatry"},"publishedOn":"2025-07-17 16:05:37","publishedOnDateReadable":"July 17th, 2025"},"versionCreatedAt":"2024-11-14 06:21:15","video":"","vorDoi":"10.1007/s00787-025-02807-5","vorDoiUrl":"https://doi.org/10.1007/s00787-025-02807-5","workflowStages":[]},"version":"v1","identity":"rs-5368250","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5368250","identity":"rs-5368250","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}