Etiology
Genetics and epigenetics
Environmental risk factors
In a Taiwan birth cohort of 309,376 singleton live births at term gestations showed an increased risk of tic disorders (6-52 weeks after birth) after exposure to particular matter with an aerodynamic diameter less than 2.5 μm \citep{Chang2022}.
\citet{Rönö2022} compared more than 5 million singletons born after the use of assisted reproductive technology (ART) with almost 5 million singletons born without the use of ART. There was not found a difference in risk of tic disorders between the groups.
In a nationwide cohort of 14,024 children and adolescents who were hospitalized with a bacterial infection with different pathogens, an increased risk of tic disorders was found when compared to controls without a bacterial infection \citep{Hsu2022}. Future studies are needed to replicate these findings.
Prenatal maternal and early childhood infections have been linked to the etiology of multiple neurodevelopmental disorders including TS (for instance, cf. \citep{Han2021}. Using several Swedish population registries, Zhand and colleagues suggest, rather surprisingly, that this might not be the case \citep{Zhang2022}. Rather, familial factors such as genetic pleiotropy may explain both the propensity to infections and and the risk to develop TS.
Pathophysiology
Pathological studies
After a hiatus of six years \citep{Lennington2016}, the group led by Flora Vaccarino return with an impressive study exploring the molecular origins of TS \citep{Brady2022}. They used pluripotent stem (iPSC)-derived organoids from patients with TS (n=5) and healthy controls obtained from punch skin biopsies and subsequent fibroblast cultures. The main results showed a mispatterning of the ventral mesencephalon in basal ganglia organoids from patients with TS with a relative lack of ventromedial progenitors accompanied by enhanced dorsolateral fates, likely due to altered GLI2/3 protein expression. The net effect seems to be a loss of medial ganglionic eminence-derived interneurons, and potentially globus pallidus projection neurons. This suggests that the interneuron loss in the basal ganglia of patients with TS \citep{Kalanithi2005}\citep{Kataoka2010} is a potential consequence of an inherent tendency of the basal ganglia to undergo a different regional specification in this condition. Also of interest was the potential implication of cilia in TS etiology. Overall, this work positions TS as a consequence of early developmental disruptions.
Neuropsychology
(Tessier 2022) compared design fluency profile of children with GTS with matched healthy controls. As a result, they have shown that children with GTS do not show general executive dysfunction in comparison to their peers.