ADHD medication adherence reduces risk of committing minor offenses in adolescents.

BACKGROUND: This study aimed to investigate the association between adolescents' adherence to attention-deficit/hyperactivity disorder (ADHD) medication and their risk of committing minor offenses. METHODS: Using two Dutch databases, Statistics Netherlands (CBS) and the Foundation for Pharmaceutical Statistics (SFK), we aimed to investigate the association between adherence to ADHD medication and registered minor offenses between 2005 and 2019 of 18,234 adolescents (12-18 years). We used Cox regression analyses to compare the rate of committing minor offenses of adolescents during periods of high ADHD medication adherence compared to periods of low adherence (i.e., periods with or without sufficient amounts of dispensed medication). We additionally tested associations with adherence to selective serotonin reuptake inhibitors (SSRIs) as control medication and analyzed potential reverse causation. RESULTS: High ADHD medication adherence was associated with a reduced risk of committing a minor offense of between 33% and 38% compared to low adherence periods of ≥3 months (hazard ratio [HR] 0.67, confidence interval [CI] 0.64-0.71) or ≥6 months (HR 0.62, CI 0.59-0.65). The reduction in risk can likely be attributed to ADHD medication, given the absence of effects of SSRIs and no reverse causation. The reduction rate remained between 16% and 55% per sex, stimulant versus non-stimulant medication, different offense categories and further sensitivity analyses. CONCLUSIONS: Among adolescents using ADHD medication, rates of criminality were lower during periods of high medication adherence, suggesting that adherence to ADHD medication may contribute to prevention of minor offenses in adolescents.

Long-Term Effectiveness of Off-Label Risperidone Treatment in Children and Adolescents: A Randomized, Placebo-Controlled Discontinuation Study.

Objectives: Risperidone is commonly prescribed off-label in children and adolescents to manage disruptive behavior. This study aimed to investigate continued benefits of risperidone after at least 1 year of treatment and effects of discontinuation on physical health. Methods: Thirty-five youths (aged 6-18 years, intelligence quotient [IQ] >70) who were treated with risperidone for at least 1 year in regular clinical practice receiving outpatient care were randomly assigned to double-blind continuation of risperidone during 16 weeks or continuation for 2 weeks, gradual dose lowering over 6 weeks, and placebo for 8 weeks. Primary outcome was the total Disruptive Behavior (D-total) score of the parent-reported Nisonger Child Behavior Rating Form-Typical IQ (NCBRF-TIQ). Secondary outcome measures were the clinician-rated Clinical Global Impressions-Improvement scale (CGI-I), the parent, child, and teacher-rated Strengths and Difficulties Questionnaire (SDQ), the parent-rated Retrospective Modified Overt Aggression Scale (R-MOAS), and several health parameters (Udvalg for Kliniske Undersøgelser Side Effect Rating Scale [UKU-SERS], dyskinesia, akathisia, parkinsonism, body mass index (BMI), waist circumference, and laboratory outcomes). Mixed models for repeated measures were conducted for continuous outcomes and a chi-square test for the CGI-I. Results: Discontinuation of risperidone, as compared with continuation, was not associated with significant changes in parent-reported disruptive behaviors. However, discontinuation was related to significant deterioration in parent-rated verbal aggression, teacher-rated behavioral functioning, clinician-rated general functioning, and significant improvements in weight, BMI, waist circumference, and glucose, insulin, and prolactin levels. Although 56% of participants in the discontinuation group experienced relapse, causing premature withdrawal from the study, 44% was able to successfully discontinue risperidone. Conclusion: Discontinuation of risperidone was associated with deterioration on some, but not all behavioral measures according to this explorative study. Discontinuation was associated with important health gains. Despite long-term benefits of risperidone, attempts to withdraw risperidone should be undertaken in individual children. This is a crucial step in preventing harm and fostering health.

The short- and longer-term effects of brief behavioral parent training versus care as usual in children with behavioral difficulties: study protocol for a randomized controlled trial.

BACKGROUND: The access to and uptake of evidence-based behavioral parent training for children with behavioral difficulties (i.e., oppositional, defiant, aggressive, hyperactive, impulsive, and inattentive behavior) are currently limited because of a scarcity of certified therapists and long waiting lists. These problems are in part due to the long and sometimes perceived as rigid nature of most evidence-based programs and result in few families starting behavioral parent training and high dropout rates. Brief and individually tailored parenting interventions may reduce these problems and make behavioral parent training more accessible. This protocol paper describes a two-arm, multi-center, randomized controlled trial on the short- and longer-term effectiveness and cost-effectiveness of a brief, individually tailored behavioral parent training program for children with behavioral difficulties. METHODS: Parents of children aged 2-12 years referred to a child mental healthcare center are randomized to (i) three sessions of behavioral parent training with optional booster sessions or (ii) care as usual. To evaluate effectiveness, our primary outcome is the mean severity of five daily ratings by parents of four selected behavioral difficulties. Secondary outcomes include measures of parent and child behavior, well-being, and parent-child interaction. We explore whether child and parent characteristics moderate intervention effects. To evaluate cost-effectiveness, the use and costs of mental healthcare and utilities are measured. Finally, parents' and therapists' satisfaction with the brief program are explored. Measurements take place at baseline (T0), one week after the brief parent training, or eight weeks after baseline (in case of care as usual) (T1), and six months (T2) and twelve months (T3) after T1. DISCUSSION: The results of this trial could have meaningful societal implications for children with behavioral difficulties and their parents. If we find the brief behavioral parent training to be more (cost-)effective than care as usual, it could be used in clinical practice to make parent training more accessible. TRIAL REGISTRATION: The trial is prospectively registered at ClinicalTrials.gov (NCT05591820) on October 24th, 2022 and updated throughout the trial.

Psychopharmacology in children and adolescents: unmet needs and opportunities.

Psychopharmacological treatment is an important component of the multimodal intervention approach to treating mental health conditions in children and adolescents. Currently, there are many unmet needs but also opportunities, alongside possible risks to consider, regarding the pharmacological treatment of mental health conditions in children and adolescents. In this Position Paper, we highlight and address these unmet needs and opportunities, including the perspectives of clinicians and researchers from the European College of Neuropsychopharmacology-Child and Adolescent Network, alongside those of experts by lived experience from national and international associations, via a survey involving 644 participants from 13 countries, and of regulators, through representation from the European Medicines Agency. We present and discuss the evidence base for medications currently used for mental disorders in children and adolescents, medications in the pipeline, opportunities in the development of novel medications, crucial priorities for the conduct of future clinical studies, challenges and opportunities in terms of the regulatory and legislative framework, and innovations in the way research is conducted, reported, and promoted.

Shared genetic etiology between ADHD, task-related behavioral measures and brain activation during response inhibition in a youth ADHD case-control study.

Impaired response inhibition is commonly present in individuals with attention-deficit/hyperactivity disorder (ADHD) and their unaffected relatives, suggesting impaired response inhibition as a candidate endophenotype in ADHD. Therefore, we explored whether behavioral and neural correlates of response inhibition are related to polygenic risk scores for ADHD (PRS-ADHD). We obtained functional magnetic resonance imaging of neural activity and behavioral measures during a stop-signal task in the NeuroIMAGE cohort, where inattention and hyperactivity-impulsivity symptoms were assessed with the Conners Parent Rating Scales. Our sample consisted of 178 ADHD cases, 103 unaffected siblings, and 173 controls (total N = 454; 8-29 years), for whom genome-wide genotyping was available. PRS-ADHD was constructed using the PRSice-2 software. We found PRS-ADHD to be associated with ADHD symptom severity, a slower and more variable response to Go-stimuli, and altered brain activation during response inhibition in several regions of the bilateral fronto-striatal network. Mean reaction time and intra-individual reaction time variability mediated the association of PRS-ADHD with ADHD symptoms (total, inattention, hyperactivity-impulsivity), and activity in the left temporal pole and anterior parahippocampal gyrus during failed inhibition mediated the relationship of PRS-ADHD with hyperactivity-impulsivity. Our findings indicate that PRS-ADHD are related to ADHD severity on a spectrum of clinical, sub-threshold, and normal levels; more importantly, we show a shared genetic etiology of ADHD and behavioral and neural correlates of response inhibition. Given the modest sample size of our study, future studies with higher power are warranted to explore mediation effects, suggesting that genetic liability to ADHD may adversely affect attention regulation on the behavioral level and point to a possible response inhibition-related mechanistic pathway from PRS-ADHD to hyperactivity-impulsivity.

Effects of positive behaviour support delivered by direct staff on challenging behaviours and quality of life of adults with intellectual disabilities: A multicentre cluster-controlled trial.

BACKGROUND: Effects of staff provided positive behaviour support (PBS) for individuals with intellectual disabilities are unclear. METHOD: Using a multicentre non-randomised cluster controlled design, 26 teams of residential group homes, including 245 staff members of 167 individuals with intellectual disabilities, were allocated to a PBS or control group. Conducting multilevel analyses (n = 123) we examined individuals' changes in irritability, other challenging behaviours and quality of life. RESULTS: Compared to controls, irritability did not significantly decrease more in the intervention group, but lethargic behaviours did. Personal development and self-determination significantly increased. Irritability of individuals in the PBS group with higher levels of irritability or lower levels of intellectual disability significantly reduced more compared to controls. CONCLUSIONS: PBS was effective in reducing irritability of individuals with severe levels of irritability or intellectual disabilities. Moreover, PBS decreased lethargic behaviours and improved several domains of quality of life.

Rare X-linked variants carry predominantly male risk in autism, Tourette syndrome, and ADHD.

Autism spectrum disorder (ASD), Tourette syndrome (TS), and attention-deficit/hyperactivity disorder (ADHD) display strong male sex bias, due to a combination of genetic and biological factors, as well as selective ascertainment. While the hemizygous nature of chromosome X (Chr X) in males has long been postulated as a key point of "male vulnerability", rare genetic variation on this chromosome has not been systematically characterized in large-scale whole exome sequencing studies of "idiopathic" ASD, TS, and ADHD. Here, we take advantage of informative recombinations in simplex ASD families to pinpoint risk-enriched regions on Chr X, within which rare maternally-inherited damaging variants carry substantial risk in males with ASD. We then apply a modified transmission disequilibrium test to 13,052 ASD probands and identify a novel high confidence ASD risk gene at exome-wide significance (MAGEC3). Finally, we observe that rare damaging variants within these risk regions carry similar effect sizes in males with TS or ADHD, further clarifying genetic mechanisms underlying male vulnerability in multiple neurodevelopmental disorders that can be exploited for systematic gene discovery.

Suicidality Treatment Occurring in Paediatrics (STOP) Medication Suicidality Side Effects Scale in young people in two cohorts across Europe.

OBJECTIVES: As part of the 'Suicidality: Treatment Occurring in Paediatrics (STOP)' study, we developed and performed psychometric validation of an electronic-clinical-outcome-assessment (eCOA), which included a patient-reported-outcome (ePRO), an observer-rated-outcome (eObsRO) for parents/carers and a clinician-reported-outcome (eClinRO) that allows identification and monitoring of medication-related suicidality (MRS) in adolescents. DESIGN: STOP: Prospective study: A two phase validation study to assess the impact of medication on suicidal ideations. SETTING: Six participating countries: Netherlands, UK, Germany, France, Spain and Italy that were part of the Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 261411. PARTICIPANTS: Cohort 1 consisted of 41 adolescent-completions, 50 parent-completions and 56 clinician-completions. Cohort 2 consisted of 244 adolescent-completions, 198 parent-completions and 240 clinician-completions from across the six countries. The scale was administered only to participants who have screened positive for the STOP-Suicidality Assessment Scale (STOP-SAS). RESULTS: A total of 24 items for the development of the STOP-Medication Suicidality Side Effects Scale (STOP-MS3) were identified and three versions (for patients, parents and clinicians) of the STOP-MS3 were developed and validated in two separate study cohorts comprising of adolescents, their parents and clinicians. Cronbach's α coefficients were above 0.85 for all domains. The inter-rater reliability of the STOP-MS3 was good and significant for the adolescent (ePRO), clinician (eClinRO) (r=0.613), parent (eObsRO) versions of the scale (r=0.394) and parent and clinician (r=0.347). Exploratory factor analysis identified a 3-factor model across 24 items for the adolescent and parent version of the scale: (1) Emotional Dysregulation, (2) Somatic Dysregulation and (3) Behavioural Dysregulation. For the clinician version, a 4-factor model defined the scale structure: (1) Somatic Dysregulation, (2) Emotional Dysregulation, (3) Behavioural Dysregulation and (4) Mood Dysregulation. CONCLUSION: These findings suggest that the STOP-MS3 scale, a web-based eCOA, allows identification and monitoring of MRS in the adolescent population and shows good reliability and validity.

Different whole-brain functional connectivity correlates of reactive-proactive aggression and callous-unemotional traits in children and adolescents with disruptive behaviors.

BACKGROUND: Disruptive behavior in children and adolescents can manifest as reactive aggression and proactive aggression and is modulated by callous-unemotional traits and other comorbidities. Neural correlates of these aggression dimensions or subtypes and comorbid symptoms remain largely unknown. This multi-center study investigated the relationship between resting state functional connectivity (rsFC) and aggression subtypes considering comorbidities. METHODS: The large sample of children and adolescents aged 8-18 years (n = 207; mean age = 13.30±2.60 years, 150 males) included 118 cases with disruptive behavior (80 with Oppositional Defiant Disorder and/or Conduct Disorder) and 89 controls. Attention-deficit/hyperactivity disorder (ADHD) and anxiety symptom scores were analyzed as covariates when assessing group differences and dimensional aggression effects on hypothesis-free global and local voxel-to-voxel whole-brain rsFC based on functional magnetic resonance imaging at 3 Tesla. RESULTS: Compared to controls, the cases demonstrated altered rsFC in frontal areas, when anxiety but not ADHD symptoms were controlled for. For cases, reactive and proactive aggression scores were related to global and local rsFC in the central gyrus and precuneus, regions linked to aggression-related impairments. Callous-unemotional trait severity was correlated with ICC in the inferior and middle temporal regions implicated in empathy, emotion, and reward processing. Most observed aggression subtype-specific patterns could only be identified when ADHD and anxiety were controlled for. CONCLUSIONS: This study clarifies that hypothesis-free brain connectivity measures can disentangle distinct though overlapping dimensions of aggression in youths. Moreover, our results highlight the importance of considering comorbid symptoms to detect aggression-related rsFC alterations in youths.

The effects of COVID-19 on child mental health: Biannual assessments up to April 2022 in a clinical and two general population samples.

Background: The COVID-19 pandemic has had an acute impact on child mental and social health, but long-term effects are still unclear. We examined how child mental health has developed since the start of the COVID-19 pandemic up to 2 years into the pandemic (April 2022). Methods: We included children (age 8-18) from two general population samples (N = 222-1333 per measurement and N = 2401-13,362 for pre-covid data) and one clinical sample receiving psychiatric care (N = 334-748). Behavioral questionnaire data were assessed five times from April 2020 till April 2022 and pre-pandemic data were available for both general population samples. We collected parent-reported data on internalizing and externalizing problems with the Brief Problem Monitor and self-reported data on Anxiety, Depressive symptoms, Sleep-related impairments, Anger, Global health, and Peer relations with the Patient-Reported Outcomes Measurement Information System (PROMIS®). Results: In all samples, parents reported overall increased internalizing problems, but no increases in externalizing problems, in their children. Children from the general population self-reported increased mental health problems from before to during the pandemic on all six PROMIS domains, with generally worst scores in April 2021, and scores improving toward April 2022 but not to pre-pandemic norms. Children from the clinical sample reported increased mental health problems throughout the pandemic, with generally worst scores in April 2021 or April 2022 and no improvement. We found evidence of minor age effects and no sex effects. Conclusions: Child mental health in the general population has deteriorated during the first phase of the COVID-19 pandemic, has improved since April 2021, but has not yet returned to pre-pandemic levels. Children in psychiatric care show worsening of mental health problems during the pandemic, which has not improved since. Changes in child mental health should be monitored comprehensively to inform health care and policy.

Sustained improvements by behavioural parent training for children with attention-deficit/hyperactivity disorder: A meta-analytic review of longer-term child and parental outcomes.

Background: Behavioural parent training is an evidence-based intervention for children with attention-deficit/hyperactivity disorder (ADHD), but little is known about the extent to which initial benefits are maintained. Aims: This meta-analytic review investigated longer-term (i.e., more than 2 months post-intervention) child and parental outcomes of behavioural parent training for children with ADHD. Materials & Methods: We searched for randomized controlled trials and examined ADHD symptoms, behavioural problems, positive parenting, negative parenting, parenting sense of competence, parent-child relationship quality, and parental mental health as outcomes. We included 27 studies (31 interventions; 217 effect sizes), used multilevel random-effects meta-analyses for between- and within-group comparisons (pre-intervention to follow-up and post-intervention to follow-up), and explored twelve predictors of change. Results: Between pre-intervention and follow-up (M = 5.3 months), we found significant small-to-moderate between-group effects of the intervention on ADHD symptoms, behavioural problems, positive parenting, parenting sense of competence and parent-child relationship quality. Within-group findings show sustained improvements in the intervention conditions for all outcome domains. There were few significant changes from post-intervention to follow-up. Additionally, the large majority of the individual effect sizes indicated sustained outcomes from post-intervention to follow-up. There were seven significant predictors of change in child outcomes, including stronger reductions in ADHD symptoms of girls and behaviour problems of younger children. In contrast with some meta-analyses on short-term effects, we found no differences between masked and unmasked outcomes on ADHD symptoms at follow-up. Discussion & Conclusion: We conclude that behavioural parent training has longer-term benefits for children's ADHD symptoms and behavioural problems, and for positive parenting behaviours, parenting sense of competence and quality of the parent-child relationship.

Difficulties in Addressing Diagnostic, Treatment and Support Needs in Individuals with Intellectual Disability and Persistent Challenging Behaviours: A Descriptive File Study of Referrals to an Expertise Centre.

Service providers may experience difficulties in providing appropriate care to optimize the functioning of individuals with intellectual disability and challenging behaviour. External consultation to identify and address the unmet support needs underlying the behaviour may be beneficial. Applying the multidimensional American Association Intellectual and Developmental Disabilities (AAIDD) model may facilitate this approach. We aimed to describe the content and outcomes of consultation for individuals with intellectual disability and challenging behaviour referred to the Dutch Centre for Consultation and Expertise in relation to the AAIDD model. Interventions were based on the clients' diagnostic, treatment, and support needs and were categorized according to the five dimensions of the AAIDD model. Outcomes of the consultations were assessed based on reports in the file and rated as 'clear improvement', 'improvement' or 'no improvement or deterioration'. In two-thirds of the 104 studied files, consultees were satisfied with the improvement in functioning. Interventions targeted the difficulties of the service providers in supporting their clients and were most often applied within the Health and Context dimensions of the AAIDD model. We may conclude that consultation of an expert team may be valuable to support the care providers, and the use of the AAIDD model may be helpful to address the unmet needs to improve the functioning of individuals with challenging behaviour.

Short-term effects of an elimination diet and healthy diet in children with attention-deficit/hyperactivity disorder: a randomized-controlled trial.

An Elimination Diet (ED) may be effective in reducing symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD), but has never been compared to an active control condition [i.e., Healthy Diet (HD)]. In a two-armed RCT, a total of N = 165 children (5-12 years) with ADHD were randomized by means of minimization (1:1) to either an ED (N = 84) or HD (N = 81) within two Dutch child and adolescent psychiatry centers. The design included a non-randomized comparator arm including N = 58 children being treated with Care as Usual (CAU). Treatment allocation was unblinded. The primary outcome was a 5-point ordinal measure of respondership based on a combination of parent and teacher ratings on ADHD and emotion regulation, determined after 5 weeks of treatment. Ordinal regression analyses were done on an intention-to-treat basis. Fewer ED (35%) than HD (51%) participants showed a partial to full response, despite overall good-to-excellent treatment adherence (> 88%) and comparable high parental prior believes. A younger age and higher problem severity predicted a better respondership. CAU-preferring participants responded more often favorably (56%) compared to ED-but not HD-participants. Small-to-medium improvements in physical health (blood pressure, heart rate, and somatic complaints) were found in response to ED/HD versus decrements in response to CAU (74% received psychostimulants). The lack of superiority of the ED versus HD suggests that for the majority of children, dietary treatment response is not rooted in food-allergies/-sensitivities. The comparable results for treatment with HD and CAU are remarkable given that CAU participants were probably 'easier to treat' than HD (and ED) participants with proportionally fewer with a (suboptimal/non-response to) prior treatment with medication (4% versus 20%). Further assessment of long-term effects is needed to evaluate the potential place of dietary treatment within clinical guidelines. The trial is closed and registered in the Dutch trial registry, number NL5324 ( https://www.onderzoekmetmensen.nl/en/trial/25997 ).

Hair Cortisol and Perceived Stress-Predictors for the Onset of Tics? A European Longitudinal Study on High-Risk Children.

Some retrospective studies suggest that psychosocial stressors trigger the onset of tics. This study examined prospective hypothalamic-pituitary-adrenal (HPA) axis activity and perceived stress prior to tic onset. In the present study, 259 children at high risk for developing tics were assessed for hair cortisol concentration (HCC) and parent-on-child-reported perceived stress four-monthly over a three-year period. We used (i) generalised additive modelling (GAM) to investigate the time effects on HCC (hair samples n = 765) and perceived stress (questionnaires n = 1019) prior to tic onset and (ii) binary logistic regression to predict tic onset in a smaller subsample with at least three consecutive assessments (six to nine months before, two to five months before, and at tic onset). GAM results indicated a non-linear increasing course of HCC in children who developed tics, and a steady HCC course in those without tics, as well as a linear-increasing course of perceived stress in both groups. Logistic regression showed that with a higher HCC in hair samples collected in a range of two to five months before tic onset (which refers to cortisol exposure in a range of four to eight months), the relative likelihood of tic onset rose. Our study suggests increased stress prior to tic onset, as evidenced by higher HCC several months before tic onset.

Adherence to Clinical Guidelines for Dose Finding and Monitoring Methylphenidate Use: A Medical Record Audit in Child and Adolescent Mental Health Care and Pediatric Settings.

Background: Guideline adherence is important to ensure optimal and safe use of methylphenidate for children and adolescents with attention-deficit/hyperactivity disorder (ADHD). We investigated adherence to Dutch guidelines regarding dosing and monitoring of methylphenidate in child and adolescent mental health care and pediatric treatment settings. Methods: Five hundred six medical records of children and adolescents were investigated in 2015 and 2016. We assessed adherence to the following guideline recommendations: (1) at least four visits during the dose-finding phase; (2) monitoring thereafter at least every 6 months; (3) measuring height and weight at least annually; and (4) the use of validated questionnaires to assess treatment response. Pearson's chi-squared test statistics were used to examine differences between settings. Results: Only a small portion of patients had at least four visits during the dose-finding phase (5.1% in the first 4 weeks to 12.4% in the first 6 weeks). Also, less than half of the patients (48.4%) were seen at least every 6 months. Height was recorded at least annually in 42.0% of patients, weight in 44.9%, and both recorded in a growth chart in 19.5%. Questionnaires to assess treatment response were only used in 2.3% of all visits. When comparing both settings, more patients in the pediatric settings were seen every 6 months, although height and weight were recorded more often in the mental health care setting. Conclusion: Overall, guideline adherence was low. Training of clinicians and adding guideline recommendations to electronic medical records templates may improve adherence. Additionally, we should aim to close the gap between guidelines and clinical practice by looking critically at the feasibility of guidelines.

Moderating Role of Depression on the Association of Tic Severity With Functional Impairment in Children.

BACKGROUND: Chronic tic disorders (CTDs) commonly co-occur with other psychiatric disorders. CTDs have been linked to functional impairment and reduction in quality of life. Insufficient research is available on depressive symptoms in patients with CTD, especially children and adolescents, yielding conflicting findings. To investigate the presence of depressive symptoms in a cohort of children and young adolescents with CTD and to test whether they moderate the link between tic severity and functional impairment. METHODS: The sample consisted of 85 children and adolescents (six to 18 years) with a CTD who were treated in a large referral center. Participants were evaluated using gold-standard self- and clinician-reporting instruments to measure tic symptom severity and tic-related functional impairment (Yale Global Tic Severity Scale), depression (Child Depression Inventory), and obsessive-compulsive symptoms (Children Yale Brown Obsessive Compulsive Scale). RESULTS: Depressive symptoms (mild to severe) were exhibited by 21% of our sample. Study participants with CTD and comorbid obsessive-compulsive disorder (OCD) and/or attention-deficit/hyperactivity disorder had higher rates of depressive symptoms compared with those without comorbidities. Significant correlations were found within and among all tic-related and OCD-related measures, yet depressive symptoms only correlated to tic-related functional impairment. Depression significantly and positively moderated the correlation between tic severity and tic-related functional impairment. CONCLUSIONS: Findings suggest that depression plays an important part as a moderator in the link between tic severity and functional impairment in children and adolescents. Our study highlights the importance of screening for and treating depression in patients with CTD.