Sensory phenomena and premonitory urge
Essing and colleagues published an important paper regarding the location of premonitory urges (PUs) in patients with tics \citep{Essing2022}. This was an online study in 291 adults with tic disorders in which participants self-reported about different characteristics of PUs. The authors found that PUs were located in the same body part or in direct proximity to the part of the body where tic was located. Most frequently, PUs were found in the area of the face and the head (62 %). Complex tics were more frequently preceded by PU than simple tics but there were no differences regarding report of PU for motor and vocal tics. Usually, PU were rather localized in the front than the back of the body (73% vs. 27%), but there were no differences between the right and left sides.
Languelage and colleagues examined urge-tic association in 25 children and adolescents with GTS. The authors were interested in urge-tic associations, including inter-individual differences, correlation with clinical measures, and compared their findings with a sample of adults. At group level the authors found positive associations between urges and tics, but this was not confirmed in the individual level data since less than half of participants showed positive association between urge and tic, similar proportion did not, and two participants had reverse association. Similarly to previous reports, associations between urge levels and tic intensity was less pronounced in children and adolescents than adults with TS \citep{Langelage2022}.
Ramsey and colleagues used structural equation modeling (SEM) to examine the distress provoked by the PU in patients with tics. Higher levels of urge intolerance predicted greater levels of clinician-rated tic severity and tic impairment \citep{Ramsey2022}.
He and colleagues tested the contribution of brain γ-aminobutyric acid (GABA) and glutamate levels of the right primary sensorimotor cortex (SM1), supplementary motor area (SMA), and insular cortex (insula) to tic and urge severity in children with TS \citep{He2022}. As a result, they demonstrated involvement of GABAergic neurotransmission within the SMA in the experience of PU in children with TS.
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. No difference was found for 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}. However, results from Sweden suggest otherwise. Indeed, 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, Zhang 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
Tesseir and colleagues compared design fluency profile of children with TS with matched healthy controls \citep{Tessier2022}. They showed that children with TS do not show general executive dysfunction in comparison to their peers .