Cholinergic mechanisms in Gilles de la Tourette's syndrome

Gilles de la Tourette syndrome (GTS), a chronic, familial, neuropsychiatric disorder of unknown etiology, is characterized clinically by the presence of motor and vocal tics that wax and wane in severity over time and by the occurrence of a variety of neurobehavioral disturbances including hyperactivity, self-mutilatory behavior, obsessive compulsive behavior, learning disabilities, and conduct disorder. Pharmacological studies suggest that the tics of GTS result from dysfunction of monoaminergic systems, more specifically from increased dopaminergic activity due to postsynaptic dopamine receptor supersensitivity. However, given that striatal dopaminergic and cholinergic systems exhibit reciprocal antagonism in other movement disorders such as Parkinsonism and chorea, it is conceivable that the cholinergic system is implicated in the disease. In the present communication it is proposed that: (a) the emergence of motor and vocal tics in GTS is associated with increased central cholinergic activity; (b) cholinergic overactivity is involved in the manifestation of other symptoms in GTS including depression, sleep disorders, motion sickness, pain, sensory tics, and the waxing and waning course of the disease; (c) abnormalities of the cholinergic system support previous evidence linking GTS with delayed cerebral maturation in a subset of young patients; and (d) drugs which stimulate cholinergic receptors may exacerbate symptoms of GTS, and as with dopamine agonists, should be avoided in patients with GTS.