Environmental risk factors

A large, full-population study from Sweden studied all singleton births in Sweden over a 30-year period, using siblings as controls \citep{28348386}. It found that "impaired fetal growth, preterm birth, breech presentation and cesarean section were associated with a higher risk of" TS or chronic tic disorder. The risks were dose-dependent, with hazard ratios rising from 1.41 for one adverse perinatal event to 2.42 for 5 or more such events. This report is important for its careful design, sample size and implications. It confirms previous indications that not all of the risk for TS is inherited, and points specifically to intrauterine and birth insults as contributing to that risk.
A nationwide study from Denmark showed that children treated with an antibiotic or admitted to a hospital for an infection had a significantly higher risk of a later diagnosis of any psychiatric illness \citep{30516814}. Interestingly, the highest risk for antibiotic use was for tic disorders, followed by OCD. (Hospitalization risk was higher for intellectual disability, though tic disorders were next highest.) The association does not prove that infections cause TS; e.g., patients destined to develop TS, or their parents, may be more likely to seek help for infections. Nevertheless, the association is interesting and deserves follow-up.

Pathophysiology

Animal models

\citep{Nespoli2018} found that dopaminergic imbalance in the dorsal striatum induced a Tourette's-like phenotype in a rodent model. Administration of quinpirole, a selective D2/D3 receptor agonist, in juvenile rats with lesions to striatal projection neurons produced movements suggestive of both simple and complex tics in the neck, limbs, and mouth. A modified YGTSS was created to comprehensively score tic-like movements based on frequency, complexity, and severity of impairment. Immunohistochemical analyses revealed significantly decreased D1 receptor RNA expression at the lesion site, consistent with the decreased striatal D1 receptor expression seen in a human post-mortem study of Tourette's \citep{Lennington2016}.  The dopaminergic imbalance induced by decreased striatal D1 receptor activity, coupled with increased D2 receptor activity, may be relevant to TS.  

Electrophysiology

Eight awake TS patients undergoing DBS electrode implantation had recordings of individual cells of the external and internal globus pallidus (GP) \citep{28556479}. Some cells in each division of the GP showed transient changes in firing rates associated with tics.

Neuroimaging studies

Mahone et al. utilized 7T spectroscopy to investigate glutamate and GABA concentrations in children with TS.  Findings included increased premotor area glutamate concentrations in TS, which also positively correlated with inhibitory control \cite{Mahone2018}.