Still in Sweden, Brander et al. \citep{Brander2019} investigated whether, at the population level, tic-related OCD has a stronger familial load than non-tic-related OCD. They found that he risk of OCD in relatives of individuals with tic-related OCD was considerably greater than the risk of OCD in relatives of individuals with non-tic-related OCD, concluding that tic-related OCD is a particularly familial subtype of OCD. The results have important implications for ongoing gene-searching efforts.
Environmental risk factors
The EMTICS study (
https://cordis.europa.eu/project/id/278367/reporting? =59137) was a large European multicenter trial investigating, among several subjects, the role of immunology in the etiology of tics, a long-discussed hypothesis in the context of PANS/PANDAS. A first paper on neuronal surface proteins on 188 patients with TS failed to confirm a link between pathogenic antibodies and causation of tics
\citep{Baglioni2019}. In line with these findings, Baumgaertel et al.
\citep{Baumgaertel2019} failed to detect autoantibodies in the CSF of 20 adult patients with TS. However, 20% of these patients had positive oligoclonal bands, an intriguing finding with no clear-cut explanation to date. Also, in the neuroimmunological field, Gilbert provides a thoughtful review of the PANDAS/PANS controversy
\citep{Gilbert2019}.
\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
Singer and Augustine have published two excellent and exhaustive reviews on the pathophysiology of tics/TS (including controversies) and the relevance for pharmacotherapy \citep*{30643668}\citep*{31319731}.
Electrophysiology
Loo et al. \citep{Loo2019} performed a 128-channel EEG study on children with TS during an exaggerated blink task and showed overall higher gamma band spectral power and differences in theta, alpha, and beta band power in inferior parietal cortex in TS children compared to controls.
Niccolai et al. \citep{Niccolai2019} studied motor-related beta oscillations in TS using magnetoencephalography and showed a biphasic increase-decrease pattern of beta oscillations. The decrease of beta oscillations was observed close to tic execution, similarly to what was observed in voluntary actions. The initial increase in beta power positively correlated with premonitory urges. Similarly, Zaparolli et al. \citep{Zapparoli2019} studied the neural activity over the sensorimotor cortex using EEG during a finger movement task in TS and found decreased levels of beta modulation compared to controls in tic-free conditions. However, the abnormal pattern normalized if the patients were actively suppressing tics during the task.
Zhu et al. \citep{Zhu2019} recorded local field potentials in the GPi and STN of patients with TS and found that beta and gamma oscillations in the GPi were restored after DBS of the GPi but not after DBS of the STN, suggesting that these oscillations may play a role in pathophysiology of persistent tics. Another study using microelectrode recordings of the STN during DBS surgery in a single TS patient was able to identify a single unit activity of the STN within the delta band which was reliably associated to optimal DBS target site for tic control \citep{Vissani2019}.
Neuroimaging studies
Ramkiran et al. \citep{31518769a} used graph theoretical measures applied to resting-state fMRI in adults with TS and studied functional properties of different portions of cortico-basal ganglia-cerebellar networks. They showed increased basal ganglia-cortical and thalamo-cortical connectivity but reduced cortico-cerebellar connectivity compared to controls. The authors also reported reductions in serial information transfer within the default mode and the salience functional networks. Altogether, the findings suggested disruption of interoceptive mechanisms and of brain maturation, as well as a shift towards excitatory neurotransmission in TS.