Linking tic disorders with infection
Tic disorders are common conditions that involve either sudden, rapid movements or vocal outbursts. These neuropsychiatric symptoms negatively affect the quality of life of patients and their families, who often require care and counselling. Scientific evidence suggests that brain circuitry and dopaminergic neurotransmission responsible for motor control and cognition are involved in tic disorders. However, the precise cellular and molecular mechanisms have to date remained elusive. The main goal of the EU-funded EMTICS (European multicentre tics in children studies) project is to elucidate the complex aetiology of tic disorders and unravel the interplay between environmental factors and genetic background. EMTICS is constructing a much-needed infrastructure for studying tic disorders and developing disease prediction models. Project partners are working under the hypothesis that tic disorders are associated with group A Streptococcus (GAS) infections and are investigating the genetic factors that may predispose some individuals to develop tics. For this purpose, they are conducting a large-scale cohort study involving affected patients and their first-degree relatives. An additional trial is investigating the effectiveness of antibiotic treatment in children with tics who are positive for GAS. Working with the mouse model, GAS-exposed mice showed increased repetitive and perseverative behaviours, and reduced concentrations of serotonin in the prefrontal cortex of the brain. They also showed significant elevations in lactate – an indicator of inflammation – in the prefrontal cortex, a brain area linked to compulsive activities and impulse control. The mice also showed evidence of active immune defence – activated microglia – in the white matter of the anterior diencephalon. These findings suggest that repeated GAS exposure may elicit inflammatory responses in brain areas involved in motor control and repetitive behaviour, resulting in behavioural and neurological abnormalities. The activities of the EMTICS study promise to generate knowledge on the aetiology and pathology of disorders like Tourette syndrome and obsessive–compulsive disorder. This will help optimise the design of targeted prevention and health care regimens. For instance, a simple administration of antibiotics combined with reduction of targeted mood-altering drugs would revolutionise treatment. This would significantly improve the quality of life of affected individuals and their families
Keywords
Tic disorders, Streptococcus infection, disease prediction models, inflammatory responses, Tourette syndrome
