ONLINE-TICS: Internet-Delivered Behavioral Treatment for Patients with Chronic Tic Disorders

Comprehensive Behavioral Intervention for Tics (CBIT) is considered a first-line therapy for tics. However, availability of CBIT is extremely limited due to a lack of qualified therapists. This study is a multicenter (n = 5), randomized, controlled, observer-blind trial including 161 adult patients with chronic tic disorders (CTD) to provide data on efficacy and safety of an internet-delivered, completely therapist-independent CBIT intervention (iCBIT Minddistrict®) in the treatment of tics compared to placebo and face-to-face (f2f) CBIT. Using a linear mixed model with the change to baseline of Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS) as a dependent variable, we found a clear trend towards significance for superiority of iCBIT (n = 67) over placebo (n = 70) (−1.28 (−2.58; 0.01); p = 0.053). In addition, the difference in tic reduction between iCBIT and placebo increased, resulting in a significant difference 3 (−2.25 (−3.75; −0.75), p = 0.003) and 6 months (−2.71 (−4.27; −1.16), p < 0.001) after the end of treatment. Key secondary analysis indicated non-inferiority of iCBIT in comparison to f2f CBIT (n = 24). No safety signals were detected. Although the primary endpoint was narrowly missed, it is strongly suggested that iCBIT is superior compared to placebo. Remarkably, treatment effects of iCBIT even increased over time.

Acute and Long-Term Effects of an Internet-Based, Self-Help Comprehensive Behavioral Intervention for Children and Teens with Tic Disorders with Comorbid Attention Deficit Hyperactivity Disorder, or Obsessive Compulsive Disorder: A Reanalysis of Data from a Randomized Controlled Trial

Attention deficit hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD) and tic disorders (TD) commonly co-occur. In addition, specific inattention difficulties and poor impulse control are related to TD in the absence of comorbid ADHD. In this study we reanalyzed data from a recently completed study comparing internet-delivered, self-help comprehensive behavioral intervention for tics (ICBIT) with a waiting-list control group. The current study describes the effects of an (ICBIT) in children and adolescents with TD with and without comorbid diagnoses of ADHD or OCD at post intervention and over three- and six-month follow-up periods. Thirty-eight 7 to 18-year-olds completed the ICBIT. Of these, 16 were diagnosed with comorbid ADHD and 11 were diagnosed with OCD. A significant improvement in tic measures was found in all groups. Both the TD + ADHD and the TD − ADHD groups were similar in the magnitude of tic reduction from baseline to post-treatment, and at the three and six-month follow-up assessments. However, the TD + OCD group benefitted less from intervention than the TD—OCD group. There were meaningful reductions in parental reports of inattention, as well as hyperactive and impulsive symptoms at post intervention and over the 6-month follow-up period. Thus, ICBIT can be effectively delivered in the presence of comorbid ADHD or OCD symptomatology and may reduce symptoms of inattention and impulsivity. Larger studies of ICBIT in children and teens with TD and comorbid ADHD and OCD are needed to optimize responses to ICBIT.

An oligogenic risk model for Gilles de la Tourette syndrome based on whole-genome sequencing data

Gilles de la Tourette syndrome (GTS) is a neurodevelopmental disorder from the spectrum of tic disorders (TDs). GTS and other TDs have a substantial genetic component with the heritability estimated at between 60 and 80%. Here we propose an oligogenic risk model of GTS and other TDs using whole-genome sequencing (WGS) data from a group of Polish GTS patients and their families (n=185). The model is based on the overrepresentation of putatively pathogenic coding and non-coding genetic variants in genes selected from a set of 86 genes previously suggested to be associated with GTS. Based on the variant overrepresentation (SKAT test results) between unrelated GTS patients and controls based on gnomAD database allele frequencies five genes (HDC, CHADL, MAOA, NAA11, and PCDH10) were selected for the risk model. Putatively pathogenic variants (n = 98) with the median allele frequency of ~0.04 in and near these genes were used to build an additive classifier which was then validated on the GTS patients and their families. This risk model successfully assigned individuals from 22 families to either healthy or GTS groups (AUC-ROC = 0.6, p < 0.00001). These results were additionally validated using the GTS GWAS data from the Psychiatric Genomic Consortium. To investigate the GTS genetics further we identified 32 genes from the list of 86 genes as candidate genes in 14 multiplex families, including NEGR1 and NRXN with variants overrepresented in multiple families. WGS data allowed the construction of an oligogenic risk model of GTS based on possibly pathogenic variants likely contributing to the risk of GTS and TDs. The model includes putatively deleterious rare and non-coding variants in and near GTS candidate genes that may cooperatively contribute to GTS etiology and provides a novel approach to the analysis of clinical WGS data.