Epidemiology

Several good epidemiological studies and meta-analyses on the childhood prevalence of TS have been published over the past years, with most figures ranging between 0.5 to 0.8%. However, prevalence in adulthood remains unknown. Levine et al. analyzed three studies (published 1986, 2011 and 2016) involving 2,356,485 participants \citep{31220521}. Overall prevalence of TS in adulthood was estimated to be 118 cases of TS per million adults, that is  0.0118%. This appears very low, even factoring in remission in two thirds to three quarters of childhood cases during adulthood (which, in itself, is debatable). Clearly, more research is needed on this important topic, preferrably using current DSM-5 criteria. 

 

Transient environmental effects on tic severity

Tic suppression

"Tic suppression in children with recent-onset tics predicts one-year tic outcome."  \citep{31241402}

Sensory phenomena and premonitory urges

A hypothesis about sensorimotor causation of tics \citep{30890965}

Other

Association with metabolic and cardiovascular disorders \citep{30640363}
A proposal for clinical staging of OCD 
Contagious yawning is suppressed when a real human is in the room (but not seen) during virtual reality (VR) presentation of yawns, but not when images of people or of recording devices were present in the VR environment \citep{30670744}.

Etiology

Family study of OCD with tics https://www.nature.com/articles/s41380-019-0532-z.epdf

Genetics

Polygenic risk scores yes, single genes no \citep{30818990}; TS-related genes expressed preferentially in DLPFC. Conclusions: "Modulation of gene expression through noncoding variants, particularly within cortico-striatal circuits, is implicated as a fundamental mechanism in Tourette’s syndrome pathogenesis. At a genetic level, tic disorders represent a continuous spectrum of disease, supporting the unification of Tourette’s syndrome and other tic disorders in future diagnostic schemata. Tourette’s PRSs derived from sufficiently large samples may be useful in the future for predicting conversion of transient tics to chronic tic disorders, as well as tic persistence and lifetime tic severity." 
ASH1L as a risk gene for TS \citep{31673123}
ADHD genes \citep{30478444}
OCD and OC symptoms linked genetically to insulin signaling \citep{Widomska_2019}
De novo gene variants related to OCD overlap with genes implicated in TS \cite{31771860}
Note: Mufford et al, 2019 GWAS markers affecting both TS risk and volumes of caudate, putamen and thalamus was included in 2018 Highlights

Epigenetics

Environmental risk factors

Maternal polycystic ovary syndrome (PCOS) is a risk for TS, ADHD and ASD \citep{30857571} 
Review of the PANDAS controversy by Don Gilbert (link)
\citet{30833232a}, using the National Health Insurance Research Database of Taiwan, analyzed 2261 TS patients and 20349 non-TS controls for the risk of traumatic brain injury (TBI). During follow-up, there was a significantly increased risk for TBI in TS patients compared to controls. Classic comorbidities such as ADHD, OCD and depression increased the risk for TBI, whereas the regular use of antipsychotic medication decreased it. These findings have important therapeutic implications. 

Pathophysiology

Animal models

 

Pathological studies

Electrophysiology

"Spatio-temporal structure of single neuron subthalamic activity in Tourette Syndrome explored during DBS procedures" \citep{Vissani_2019}.
Cued voluntary eye blinking studied by EEG in people with and without tics \citep{31382238}.

Neuroimaging studies

SERT binding increased in people with TS+OCD \citep{30700759}
Boys with anxiety disorders have altered WM in the uncinate fasciculus \citep{30654645}
The ENIGMA-OCD group was able to use their very large data set to show that individual subject "mega-analysis" is superior to a site-wise meta-analysis \citep{30670959}. This result will guide the nascent ENIGMA-TS group.
fcMRI study \citep{Nielsen2020}
(Ramkiran et al., 2019) 
Insula, premonitory urges, MRI https://www.researchgate.net/publication/338388423_The_role_of_the_insula_in_the_generation_of_motor_tics_and_the_experience_of_the_premonitory_urge-to-tic_in_Tourette_syndrome  cf. 
Cerebellum https://www.researchgate.net/publication/338388303_STRUCTURE_AND_COVARIANCE_OF_THE_GREY_MATTER_IN_THE_CEREBELLUM_IN_YOUNG_PEOPLE_WITH_TOURETTE_SYNDROME

Pharmacological studies

"to assess reactive inhibitory control in adult TD patients with and without antipsychotic medication, and under emotional stimulation (visual images with positive, neutral and negative content)." DOI 10.1016/j.cortex.2019.12.007

Clinical and neuropsychological studies

Young adults with TS showed reduced accuracy in the second step of a reaching task, consistent with a model in which forward updating of a model of the movement is abnormal \citep{30561518}.
Martino et al cerebellar timing task ( https://doi.org/10.3389/fneur.2019.00385 ) .
"A superior ability to suppress fast inappropriate responses in children with Tourette syndrome is further improved by prospect of reward" \citep{31103639}.

Other

 

Treatment

In a large study of manualized CBT in children with OCD, anxious and depressive symptoms improved substantially and was not linked to improvements in OCD severity [  10.1016/j.psychres.2019.04.021 ]. This result is one more argument in favor of psychotherapy for obsessions and compulsions, which are common in people with tics. A consensus report argues strongly for early intervention in OCD \citep{30773387}. Since early-onset OCD is associated with tics \cite{21820387}, a similar argument could be made for early intervention in tic disorders, especially since effective behavioral treatments without side effects are available. Studies of whether early intervention changes the course of tic disorders are needed.
 

Psychological interventions

One of the most interesting possibilities in delivering CBT for tics has come from the development of intrenet-based platforms, making these approaches available for a large numebr of patients, even in remote areas. The BIP-TIC platform, developed in Sweden, allows to use either HRT, ERP or a mixture of both online with a possible intervention of a therapist by phone or email. A first pilot study on 23 patients has shown encouraging results in a rater-blind parallel group trial (including a 12 month follow up)  \citep{30772854}. A large (n= +200) UK-based study using this platform, and focussing on en ERP-based methodolody, called ORBIT, will commence shortly \citep{30610027}.
CBIT-Jr \citep{Bennett_2019}
 

Medication

 

Neurosurgery