Neuropsychiatric symptoms in siblings of children with Tourette syndrome in the EMTICS study

Abstract

Background: Tourette syndrome (TS) is associated with neuropsychiatric comorbidities, such as autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD). Even though comorbidities are the main source of impairment in individuals with TS, family aggregation between TS and other neuropsychiatric disorders has been little explored. We therefore investigated associations of tic severity in probands with symptoms of ASD, ADHD, and ODD in their siblings and the influence of tic severity, age, and sex.

Methods: The sample of the present study stems from the European Multicenter Tics in Children Study (EMTICS), a longitudinal observational study, with the present subsample of 196 probands with TS and their 220 full siblings (54.1% girls). We analyzed associations of probands' tic severity with ASD, ADHD, and ODD symptoms in their siblings using generalized linear mixed-effect negative binomial regression models.

Results: Higher tic severity in probands was associated with higher scores of ASD symptoms in their siblings (IRR = 1.48, 95% confidence interval [95% CI] 1.03-2.12, p = 0.034); after excluding the three items in the Autism Spectrum Screening Questionnaire linked to stereotypies (that may be misinterpreted as tic-like behaviors; IRR = 1.44 [95% CI] 0.99-2.09, p = 0.057) the effect size remained similar, yet reaching only near-significance. Moreover, we demonstrated a significant interaction between probands' tic severity and sex upon siblings' symptoms of ADHD and ODD. Female siblings of probands with higher tic severity displayed more symptoms of ADHD and ODD, whereas this effect was absent in male siblings.

Conclusions: This multicenter study demonstrated a link between probands' current tic severity and siblings' neuropsychiatric symptoms. Our study suggests a familial link between TS and ASD-like symptoms, competencies as well as sex-specific associations with ADHD and ODD symptoms in female siblings. The current study sheds light on a broader family tendency and highlights the need for targeted prevention in this vulnerable population. Our findings, however, call for further studies to better understand the genetic and environmental aggregation of influences between individuals with TS, ADHD, and ODD and their siblings.

Keywords: ADHD; ODD; Tourette syndrome; autism spectrum disorder; siblings.

FIGURE 1

Interaction plot between the proband’s tic severity and the sex of the sibling upon the Swanson, Nolan and Pelham‐version IV rating scale (SNAP‐IV) hyperactivity/impulsivity severity score. For girls, there was a significant positive association between proband’s tic severity and the siblings’ hyperactivity/impulsivity symptoms. However, for boys, even if there is a decreasing slope, the association was not statistically significant.

FIGURE 2

Interaction plot between the proband’s tic severity and the sex of the sibling upon the Swanson, Nolan and Pelham‐version IV rating scale (SNAP‐IV) inattention severity score. For girls, there was a significant positive association between proband’s tic severity and the siblings’ inattention symptoms. However, for boys, even if there is a decreasing slope, the association was not statistically significant.

FIGURE 3

Interaction plot between the proband’s tic severity and the sex of the sibling upon the SNAP oppositional defiant disorder (ODD) severity score. For girls, there was a significant positive association between proband’s tic severity and the siblings’ ODD symptoms. However, for boys, even if there was a trend with a decreasing slope, the association was not statistically significant.