Neuroimmunoendocrinology of Tourette Syndrome

Abstract Cellular and molecular mechanisms involving immune-competent cells can modulate normal brain development, influencing the genesis, refinement, and maintenance of neural circuits. There is increasing evidence in support of the contribution of an early immune priming to the abnormal trajectories of maturation of cortico-subcortical circuits associated with the generation of tics. During postnatal life, the hyperreactivity of systemic immune pathways and neuroinflammation may contribute to natural fluctuations of the behavioral features manifesting in Tourette syndrome and related disorders. Moreover, abnormalities in the parallel development of neural and immune systems, as well as in stress responses, are reflected in the higher risk of autoimmune and allergic illnesses in people with these neurodevelopmental disorders. There is still limited knowledge regarding the efficacy of direct and indirect immune-modulatory interventions in the treatment of these disorders. There are also limitations in knowledge of the key molecular pathways associated with gut dysbiosis that can influence neuroimmune interactions in these disorders. This chapter provides an up-to-date summary of the existing knowledge around these themes, highlighting existing gaps that need to be addressed by future research in order to develop breakthrough, disease-modifying, immunological, hormonal, and microbiota-based therapeutic interventions.